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1.
J Immunol Res ; 2022: 5398743, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35996623

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized, among others, by tissue damage and activation/differentiation of proinflammatory lymphocytes. Accordingly, several studies have concluded that type 17 T helper (Th17) cells seem to have an important role in the pathogenesis of this condition. However, the strategy for the identification and analysis of proinflammatory Th17 cells in those studies has not been consistent and has usually been different from what was originally described. Therefore, we decided to evaluate the levels of Th17 cells in patients with RA employing an extended immune phenotype by using an eight-color multiparametric flow cytometry analysis. For this purpose, blood samples were obtained from 30 patients with RA and 16 healthy subjects, and the levels of Th17 and type 22 helper (Th22) lymphocytes were analyzed as well as the in vitro differentiation of peripheral blood mononuclear cells into Th17 lymphocytes induced by interleukin-23 (IL-23) and IL-1ß. We found significant enhanced levels of total Th17 lymphocytes (defined as CD4+IL-17+) as well as enhanced numbers of their pathogenic (defined as CD4+CXCR3+IL-17+IL-22+CD243+CD161+IFN-γ +IL-10-) and nonpathogenic (CD4+CXCR3+IL-17+IL-22-CD243-CD161-IFN-γ -IL-10+) cell subsets in patients with RA. Likewise, the number of Th22 (CD4+CXCR3+/-IL-17-IL-22+) was also increased in these patients compared to healthy controls. However, the in vitro induction/differentiation of pathogenic Th17 cells showed similar results in controls and patients with RA. Likewise, no significant associations were detected in patients with RA between the levels of Th17 or Th22 cells and clinical or laboratory parameters. Our data indicate that patients with RA show enhanced blood levels of the different subsets of Th17 cells and Th22 lymphocytes tested in this study and suggest that these levels are not apparently associated with clinical or laboratory parameters.


Assuntos
Artrite Reumatoide , Células Th17 , Humanos , Interleucina-10 , Interleucina-17 , Interleucinas , Leucócitos Mononucleares , Células Th1
2.
Clin Exp Immunol ; 209(1): 115-125, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35576512

RESUMO

A low-grade inflammatory phenomenon is a feature of overweight and metabolic syndrome. The involvement of a pro-inflammatory Th17 lymphocyte subset and the CD69+ T regulatory (Treg) cell subtype in patients with metabolic dysfunction associated with or without overweight has not been fully elucidated. The aim of this study was to perform a quantitative and functional analysis of pathogenic Th17 lymphocytes and CD69+ Treg cells in patients with metabolic dysfunction (insulin resistance and dyslipidemia). The number of pathogenic Th17 cells and the levels and function of CD69+ Treg cells were analyzed in blood samples from individuals with metabolic dysfunction, associated with or without overweight. Pathogenic and non-pathogenic Th17 lymphocytes as well as Th22 cells were determined by eight-color flow cytometry analysis, whereas the levels and suppressive function of CD69+ Treg cells were also analyzed by multiparametric flow cytometry. We detected increased levels of pro-inflammatory Th17 pathogenic cells and Th22 lymphocytes in overweight unhealthy individuals (P < 0.001, compared to normal weight healthy). Conversely, diminished numbers of CD69+ Treg lymphocytes were observed in metabolically unhealthy individuals, with or without overweight. Likewise, the immunosuppressive function of CD69+ Treg cells was also defective in these patients. The increased levels of pathogenic Th17 cells along with a diminished number and function of CD69+ Treg lymphocytes may significantly contribute to the low-grade inflammatory phenomenon of metabolically unhealthy patients.


Assuntos
Linfócitos T Reguladores , Células Th17 , Citometria de Fluxo , Humanos , Subpopulações de Linfócitos , Sobrepeso/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo
3.
J Immunol Res ; 2018: 9627806, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30116758

RESUMO

We assessed different immune parameters in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with low (LSI) and high (HSI) sodium intake. Thirty-eight patients with RA, thirty-seven with SLE, and twenty-eight healthy subjects were studied and classified as LSI or HSI. Levels and suppressive function of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells were determined by flow cytometry in blood samples. Levels and in vitro differentiation of Th17 cells were also assessed. Similar levels of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells were observed in LSI and HSI patients or controls. However, a positive correlation was detected between sodium intake and levels of CD4+CD25+Foxp3+ Treg cells in SLE and a negative association between CD4+CD69+Foxp3- Treg cells and sodium intake in RA. No other significant associations were detected, including disease activity and sodium intake. Moreover, the suppressor activity of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells was similar in LSI and HSI patients or controls. The levels and in vitro differentiation of Th17 cells were also similar in LSI and HSI individuals. Our results suggest that, in the population studied (Mexican mestizo), the level of sodium intake is not apparently associated with different relevant immune parameters in healthy subjects or patients with SLE or RA.


Assuntos
Artrite Reumatoide/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Cloreto de Sódio na Dieta/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Mediators Inflamm ; 2017: 2513829, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29038617

RESUMO

T regulatory (Treg) cells have a key role in the pathogenesis of chronic inflammatory and autoimmune diseases. A CD4+CD69+ T cell subset has been described that behaves as Treg lymphocytes, exerting an important immune suppressive effect. In this study, we analyzed the levels and function of CD4+CD69+ Treg cells in patients with systemic lupus erythematosus (SLE). Blood samples were obtained from 22 patients with SLE and 25 healthy subjects. Levels of CD4+CD69+ Treg cells were analyzed by multiparametric flow cytometry, and their function was measured by an assay of suppression of lymphocyte activation and through the inhibition of cytokine synthesis. We found an increased percent of CD4+CD25varCD69+TGF-ß+IL-10+Foxp3- lymphocytes in patients with SLE compared to controls. In addition, a significant diminution in the suppressive effect of these cells on the activation of autologous T lymphocytes was observed in most patients with SLE. Accordingly, CD69+ Treg cells from SLE patients showed a defective capability to inhibit the release of IL-2, IL-6, IL-10, and IL-17A by autologous lymphocytes. Our findings suggest that while CD4+CD69+ Treg lymphocyte levels are increased in SLE patients, these cells are apparently unable to contribute to the downmodulation of the autoimmune response and the tissue damage seen in this condition.


Assuntos
Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Adolescente , Adulto , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/metabolismo , Adulto Jovem
5.
Rev Invest Clin ; 69(1): 5-10, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28239176

RESUMO

BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease whose cause has not been fully elucidated. However, genetic factors seem to have an important role in its pathogenesis. OBJECTIVE: We analyzed the possible association between rheumatoid arthritis and variants of the SLC11A1 gene, which encodes for NRAMP1, a protein involved in the activation of phagocytes and synthesis of proinflammatory cytokines. METHODS: In a case-control study in a Mexican Mestizo population, blood samples from 188 patients with rheumatoid arthritis and 133 healthy individuals were obtained to determine the frequency of SLC11A1 gene variants INT4 (469+14G/C or rs3731865), D543N (1730G/A or rs17235409) and 3'UTR (1729+55del4 or rs17235416) by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: We found similar frequencies of INT4 and 3'UTR polymorphisms in patients and controls (p = 0.18 and 0.89, respectively). In contrast, a significantly lower frequency of the D543N polymorphism was observed in patients with rheumatoid arthritis compared to controls (p corrected = 0.016; OR: 0.48; 95% CI: 0.28-0.80). CONCLUSION: Our data suggest that the D543N variant of SLC11A1 gene has a protective effect in the development of rheumatoid arthritis, an interesting finding that has not been previously reported in any population.


Assuntos
Artrite Reumatoide/genética , Proteínas de Transporte de Cátions/genética , Etnicidade/genética , Predisposição Genética para Doença/etnologia , Adolescente , Adulto , Artrite Reumatoide/etnologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Masculino , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Adulto Jovem
6.
J Oral Pathol Med ; 46(7): 549-557, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27759906

RESUMO

BACKGROUND: Periodontal disease is chronic inflammatory process that affects the attachment structures of the teeth and constitutes a significant cause of tooth loss in adults. Although different bacteria play an important role in the triggering of this condition, the progression and severity of the disease are strongly affected by the host immune response, which is under the control of different immune regulatory mechanisms, including T regulatory (Treg) cells. The aim of this study was to assess the frequency and function of CD69+ Treg lymphocytes in patients with chronic periodontal disease. METHODS: Peripheral blood samples (n = 33) and gingival tissue (n = 9) were obtained from patients with chronic periodontal disease. Blood samples from 25 healthy individuals were also studied. Levels of CD69+ Treg lymphocytes in peripheral blood and gingival tissue were determined by six-color multiparametric flow cytometry, immunofluorescence, and immunohistochemistry. The immune regulatory function of CD69+ Treg cells was tested by an in vitro assay of inhibition of lymphocyte activation. RESULTS: Percentages of CD69+ Treg cells were significantly higher in the peripheral blood from patients with active periodontal disease compared to healthy controls, and these percentages inversely correlated with the periodontal attachment loss. Increased numbers of these Treg cells were detected in the gingival tissue from active PD patients compared to their peripheral blood. However, the suppressive function of CD69+ Treg cells was significantly diminished in patients with periodontal disease compared to healthy controls. CONCLUSIONS: Our data suggest that CD69+ Treg cells seem to be another important piece in the complex immunopathogenesis of periodontal disease.


Assuntos
Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/imunologia , Lectinas Tipo C/imunologia , Doenças Periodontais/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Feminino , Gengiva/imunologia , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade
7.
J Immunol Res ; 2016: 4163094, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27057555

RESUMO

Dendritic cells (DC) play an important role in the development and maintenance of immune tolerance. Although the inhibitory receptor ILT4/LILRB2 has been related with the tolerogenic phenotype of DC, the possible role of this receptor in the breakdown of DC tolerogenic function in systemic lupus erythematosus (SLE) has not been elucidated. In this study, we analyzed the expression and function of the inhibitory receptor ILT4 in DC from SLE patients. We found that the percentage of ILT4 positive plasmacytoid DC and myeloid DC is significantly diminished in SLE patients. Interestingly, ligation of ILT4 did not affect the maturation or immunogenic capability of DC in healthy controls. In contrast, in SLE patients we observed an inhibitory effect of ILT4 on the immunogenic capability of DC. ILT4 was shown not to have a crucial role in regulating the maturation and function of DC from healthy controls but is partially involved in the maturation process and immunogenic capability of DC from SLE patients, suggesting that other inhibitory receptors, involved in the regulation of DC tolerogenic function, may be impaired in this autoimmune disease.


Assuntos
Células Dendríticas/imunologia , Tolerância Imunológica , Lúpus Eritematoso Sistêmico/imunologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Adulto , Antígenos CD/imunologia , Antígenos CD/metabolismo , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Feminino , Humanos , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Lipopolissacarídeos/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Glicoproteínas de Membrana/imunologia , Fenótipo , Receptores Imunológicos/imunologia
8.
Reumatol. clín. (Barc.) ; 11(5): 316-321, sept.-oct. 2015. ilus
Artigo em Espanhol | IBECS | ID: ibc-140340

RESUMO

Las prevalencia de las alteraciones nutricionales en pacientes con enfermedades reumatológicas varía entre un 4 y un 95%, dependiendo del método empleado para su detección. Inicialmente agrupadas bajo el término de caquexia reumatológica, en la actualidad es posible ampliar el concepto de desnutrición conforme los mecanismos fisiopatológicos que participan, sea desnutrición asociada a procesos inflamatorios crónicos (caquexia), desnutrición asociada a procesos inflamatorios agudos (desnutrición proteico-calórica) y desnutrición asociada a baja ingesta alimentaria. El espectro clínico de la desnutrición asociada a enfermedades reumatológicas varía desde el paciente con bajo peso hasta el paciente con sobrepeso u obesidad, con disminución en la cantidad de masa magra, repercusión funcional, en calidad de vida y pronóstico, como común denominador. Adicionalmente, el incremento asociado en masa grasa aumenta el riesgo para el desarrollo de enfermedad cardiovascular. El manejo integral de las enfermedades reumatológicas debe de incluir aspectos para la prevención, la identificación y el manejo oportunos de las alteraciones nutricionales (AU)


The prevalence of nutritional alterations in rheumatologic diseases ranges from 4 to 95%, depending on the detection method used. Formerly described as the single term rheumatoid cachexia, nutritional alterations can currently be grouped and subdivided based on the physiopathological mechanisms involved: chronic disease-related inflammatory conditions (cachexia), malnutrition associated to acute malnutrition inflammatory conditions (protein-caloric malnutrition) and starvation-related malnutrition. Clinical manifestations of malnutrition associated to rheumatic diseases vary from the patient with low weight or overweight and obesity; with lean body mass depletion as well as functional repercussions, and impact of quality of life as a common denominator. Additionally, the associated increase in body fat mass increases the risk for cardiovascular morbidity. A multidisciplinary approach towards rheumatic diseases should include aspects oriented towards prevention, early identification, diagnosis and correction of nutritional alterations (AU)


Assuntos
Feminino , Humanos , Masculino , Caquexia/complicações , Caquexia/dietoterapia , Fenômenos Fisiológicos da Nutrição , Distúrbios Nutricionais/complicações , Distúrbios Nutricionais/dietoterapia , Doenças Reumáticas/complicações , Doenças Reumáticas/dietoterapia , Doenças Reumáticas/fisiopatologia , Avaliação Nutricional , Obesidade/complicações , Obesidade/dietoterapia , Sobrepeso/complicações , Sobrepeso/dietoterapia , Sarcopenia/complicações , Sarcopenia/dietoterapia , Qualidade de Vida
9.
Reumatol Clin ; 11(5): 316-21, 2015.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26094123

RESUMO

The prevalence of nutritional alterations in rheumatologic diseases ranges from 4 to 95%, depending on the detection method used. Formerly described as the single term rheumatoid cachexia, nutritional alterations can currently be grouped and subdivided based on the physiopathological mechanisms involved: chronic disease-related inflammatory conditions (cachexia), malnutrition associated to acute malnutrition inflammatory conditions (protein-caloric malnutrition) and starvation-related malnutrition. Clinical manifestations of malnutrition associated to rheumatic diseases vary from the patient with low weight or overweight and obesity; with lean body mass depletion as well as functional repercussions, and impact of quality of life as a common denominator. Additionally, the associated increase in body fat mass increases the risk for cardiovascular morbidity. A multidisciplinary approach towards rheumatic diseases should include aspects oriented towards prevention, early identification, diagnosis and correction of nutritional alterations.


Assuntos
Caquexia/etiologia , Desnutrição/etiologia , Obesidade/etiologia , Doenças Reumáticas/complicações , Caquexia/diagnóstico , Caquexia/terapia , Humanos , Desnutrição/diagnóstico , Desnutrição/terapia , Obesidade/diagnóstico , Obesidade/terapia , Doenças Reumáticas/fisiopatologia
10.
Clin Dev Immunol ; 2013: 584303, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24288552

RESUMO

Dendritic cells (DCs) have a key role in the regulation of immune response. We herein explored, in patients with inflammatory diseases, the role of monocyte derived DC's (mo-DCs) on the generation of Th17 and T regulatory (Treg) lymphocytes. Peripheral blood was obtained from thirty-five patients with rheumatoid arthritis (RA), twelve with systemic lupus erythematosus (SLE), and twenty healthy subjects. Mo-DCs were generated under standard (IL-4/GM-CSF) or tolerogenic (IL-4/GM-CSF plus recombinant P-selectin or PD-1 or IL-10) conditions, and their ability to induce Th17 and Treg lymphocytes was tested. We detected that mo-DCs from patients with RA showed an enhanced release of IL-6 and IL-23 as well as an increased capability to induce Th17 cells. Although mo-DCs from SLE patients also released high levels of IL-6/IL-23, it did not show an increased ability to induce Th17 lymphocytes. In addition, mo-DCs, from patients with RA and SLE generated under the engagement of PSGL-1, showed a defective capability to induce Foxp3+ Treg cells. A similar phenomenon was observed in SLE, when DC's cells were generated under PDL-1 engagement. Our data indicate that DCs from patients with rheumatic inflammatory disease show an aberrant function that may have an important role in the pathogenesis of these conditions.


Assuntos
Artrite Reumatoide/imunologia , Células Dendríticas/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adolescente , Adulto , Artrite Reumatoide/metabolismo , Diferenciação Celular , Técnicas de Cocultura , Citocinas/metabolismo , Células Dendríticas/metabolismo , Feminino , Humanos , Imunofenotipagem , Lúpus Eritematoso Sistêmico/metabolismo , Pessoa de Meia-Idade , Fenótipo , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo , Células Th17/citologia , Células Th17/metabolismo , Adulto Jovem
11.
J Clin Immunol ; 33(2): 368-77, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23097038

RESUMO

The aim of this work was to study the expression and function of the innate immune receptor dectin-1 in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We studied twenty-six patients with SLE not receiving immunosuppressive therapy, twenty-six patients with RA, and fifteen controls. We found that monocytes from SLE patients showed a diminished expression of dectin-1 compared to healthy controls, and an inverse correlation between percent of dectin-1(+) cells and the disease activity score was detected. In addition, cells from SLE patients showed an abnormal calcium flux response induced by dectin-1 ligands as well as an enhanced release of IL-1ß, IL-6 and TNF-α, but not IL-23, upon dectin-1 engagement. Monocytes from patients with RA also showed a diminished expression, and a defective function of dectin-1. Our data suggest that dectin-1 receptor defects could contribute to the pathogenesis of autoimmune inflammatory conditions.


Assuntos
Artrite Reumatoide/metabolismo , Lectinas Tipo C/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Monócitos/metabolismo , Adulto , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Citocinas/biossíntese , Feminino , Regulação da Expressão Gênica , Humanos , Imunofenotipagem , Lectinas Tipo C/genética , Lúpus Eritematoso Sistêmico/genética , Masculino , Monócitos/imunologia , Adulto Jovem
12.
J Clin Immunol ; 31(4): 588-95, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21487894

RESUMO

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease. Natural T regulatory (nTreg) cells, which constitutively express the CTLA-4 molecule, have an important role in the pathogenesis of autoimmune conditions. Although it has been reported that biological agents are able to modulate the levels or function of Treg lymphocytes, the possible effect of Abatacept (CTLA-4-Ig) therapy on these cells has not been studied in autoimmune conditions. We explored the effect of Abatacept therapy on Treg cells in patients with RA. The number of different subsets of Treg cells was analyzed by flow cytometry in the peripheral blood from 45 patients with RA that were (n = 30) or not (n = 15) under Abatacept therapy as well as in 20 healthy controls. The function of Treg cells was assessed by an assay of inhibition of lymphocyte proliferation. We found that Abatacept therapy was associated with a significant diminution in the levels of CD4+CD25(bright)Foxp3+, and CD4+CTLA-4+ nTreg cells. In contrast, the regulatory function of CD4+CD25+ lymphocytes was significantly enhanced after the administration of Abatacept. Our data suggest that CTLA-4-Ig exerts a complex and interesting effect on Treg cells in patients with RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Imunoconjugados/uso terapêutico , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Abatacepte , Adolescente , Adulto , Artrite Reumatoide/patologia , Antígenos CD4/imunologia , Proliferação de Células , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/metabolismo , Subunidade alfa de Receptor de Interleucina-2/imunologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/patologia
13.
Immunopharmacol Immunotoxicol ; 33(1): 169-77, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20536340

RESUMO

CONTEXT: T regulatory (Treg) cells play an important role in the modulation of the immune response, and are implicated in the pathogenesis of autoimmune diseases. Many people is exposed to fluoride (F), mainly through drinking water. OBJECTIVE: The aim of this work was to assess the possible effect of F exposure on different immune parameters, mainly Treg cells. MATERIALS AND METHODS: We studied 61 subjects from a community of the state of Durango, Mexico, where the population is exposed to F levels over 2.0 ppm in drinking water. Peripheral blood mononuclear cells (PBMC) were isolated and the level and function of Treg cells was analyzed by flow cytometry and cell proliferation assays. In addition, we detected the presence of apoptotic cells, the expression of TLR/CD14, and the in vitro synthesis of TNF-α by monocytes. RESULTS: We found a negative correlation between urinary F and percentage of CD4(+)CD25(+) Treg cells (r = -0.55, P < 0.001). Accordingly, a defective function of these cells was detected in 30% of individuals exposed to F. In contrast, a positive association between levels of CD4(+)TGF-ß(+) or CD4(+)IL-10(+) Treg lymphocytes and F urine concentrations was detected. In addition, a negative correlation was detected between the F urinary levels and the proportion of apoptotic cells, in PBMC or T cells or monocytes (P < 0.05 in all cases). Finally, no apparent association between F exposure and TLR4/CD14 expression or the synthesis of TNF-α was detected. CONCLUSION: Our data suggest that F exposure exerts a complex and relevant effect on Treg cells in humans.


Assuntos
Exposição Ambiental/efeitos adversos , Fluoretos/efeitos adversos , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Poluentes Químicos da Água/efeitos adversos , Adolescente , Adulto , Idoso , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Contagem de Linfócito CD4 , Proliferação de Células/efeitos dos fármacos , Estudos Transversais , Exposição Ambiental/análise , Feminino , Citometria de Fluxo , Fluoretos/urina , Humanos , Masculino , México , Pessoa de Meia-Idade , Vigilância da População , Inquéritos e Questionários , Poluentes Químicos da Água/urina , Adulto Jovem
14.
J Clin Immunol ; 31(3): 369-78, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21188486

RESUMO

Human leukocyte antigen (HLA)-G is a class I non-classical HLA molecule with an important regulatory role on the immune response. The possible role of this molecule in the pathogenesis of SLE has not been explored. In this work, we evaluated the expression and function of HLA-G in SLE patients. We studied 37 SLE patients as well as 25 healthy donors. Peripheral blood monocytes and in vitro-generated dendritic cells (DCs) were analyzed for HLA-G expression by flow cytometry. We found that monocytes from SLE patients as well as mature CD83+ DCs showed a diminished expression of HLA-G compared with healthy controls. In addition, monocytes from SLE patients showed a diminished induction of HLA-G expression in response to stimulation with IL-10. Furthermore, functional assays showed that these monocytes pre-treated with IFN-γ exhibited a diminished capability to inhibit the proliferation of autologous lymphocytes. Finally, lymphocytes from SLE patients tended to display a lower acquisition of HLA-G (by trogocytosis) from autologous monocytes compared to controls. Our results might have implications for the immune abnormalities observed in patients with SLE.


Assuntos
Células Dendríticas/metabolismo , Expressão Gênica/imunologia , Antígenos HLA-G , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos/metabolismo , Monócitos/metabolismo , Adulto , Antígenos CD/análise , Antígenos CD/imunologia , Estudos de Casos e Controles , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/patologia , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Antígenos HLA-G/genética , Antígenos HLA-G/imunologia , Antígenos HLA-G/metabolismo , Humanos , Imunoglobulinas/análise , Imunoglobulinas/imunologia , Técnicas In Vitro , Interferon gama/sangue , Interferon gama/imunologia , Interferon gama/farmacologia , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-10/farmacologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Ativação Linfocitária , Linfócitos/imunologia , Linfócitos/patologia , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/imunologia , Monócitos/imunologia , Monócitos/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Antígeno CD83
15.
Eur J Immunol ; 40(5): 1418-27, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20201038

RESUMO

Human cytomegalovirus (hCMV) infection is usually asymptomatic but may cause disease in immunocompromised hosts. It has been reported that hCMV infection may shape the NK cell receptor (NKR) repertoire in adult individuals, promoting a variable expansion of the CD94/NKG2C+ NK cell subset. We explored the possible relationship between this viral infection and the expression pattern of different NKR including CD94/NKG2C, CD94/NKG2A, immunoglobulin-like transcript 2 (ILT2, CD85j), KIR2DL1/2DS1, KIR3DL1, and CD161 in peripheral blood lymphocytes from healthy children, seropositive (n=21) and seronegative (n=20) for hCMV. Consistent with previous observations in adults, a positive serology for hCMV was associated with increased numbers of NKG2C+ NK and T cells as well as with ILT2+ T lymphocytes. Moreover, the proportions of CD161+ and NKG2C+CD56-CD3- NK cells also tended to be increased in hCMV+ individuals. Excretion of the virus was associated with higher proportions of NKG2C+ NK cells. Altogether, these data reveal that hCMV may have a profound influence on the NKR repertoire in early childhood.


Assuntos
Infecções por Citomegalovirus/imunologia , Regulação Viral da Expressão Gênica , Células Matadoras Naturais/imunologia , Receptores de Células Matadoras Naturais/biossíntese , Anticorpos Antivirais/sangue , Antígenos CD/biossíntese , Antígenos CD/genética , Criança , Pré-Escolar , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/urina , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Células Matadoras Naturais/classificação , Células Matadoras Naturais/metabolismo , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Masculino , Subfamília B de Receptores Semelhantes a Lectina de Células NK/biossíntese , Subfamília B de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília C de Receptores Semelhantes a Lectina de Células NK/biossíntese , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília D de Receptores Semelhantes a Lectina de Células NK/biossíntese , Subfamília D de Receptores Semelhantes a Lectina de Células NK/genética , Receptores Imunológicos/biossíntese , Receptores Imunológicos/genética , Receptores de Células Matadoras Naturais/genética , Saliva/virologia , Urina/virologia
16.
J Autoimmun ; 27(2): 110-8, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16890406

RESUMO

Regulatory T cells have an important role in the control of self-reactivity, and in the pathogenesis of autoimmune inflammatory conditions. The aim of this work was to perform a quantitative and functional analysis of regulatory T cells in patients with systemic lupus erythematosus (SLE). We studied twenty-three patients with SLE (19 active, 4 inactive), and twenty-seven healthy subjects as well as fifteen patients with rheumatoid arthritis (RA). The following cell subsets were analyzed in peripheral blood mononuclear cells by flow cytometry: CD4+CD25+, CD4+CD25(bright), CD4+Foxp3+ (Treg cells), CD8+CD28- (Ts cells), CD4+IL-10+ (Tr1 cells), and CD4+TGF-beta+ (Th3 cells). In addition, the in vitro suppressive activity of CD4+CD25+ lymphocytes was tested. We found no significant differences in the levels of all regulatory cell subsets studied in SLE patients compared to controls and RA patients. However, a defective regulatory function of CD4+CD25+T cells was observed in a significant fraction (31%) of patients with SLE. Our data indicate that although approximately one third of patients with SLE show an abnormal immunosuppressive function of Treg lymphocytes, their levels of the different regulatory T cell subsets in peripheral blood are not significantly different from those found in controls.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Artrite Reumatoide/imunologia , Feminino , Citometria de Fluxo , Humanos , Interleucina-10/biossíntese , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/biossíntese
17.
Arthritis Res Ther ; 8(3): R83, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16677395

RESUMO

We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5 to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition, the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia, no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (TREG, Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for TREG cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of TREG cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/imunologia , Adulto , Anticorpos Monoclonais Murinos , Antirreumáticos/uso terapêutico , Apoptose , Linfócitos T CD4-Positivos/imunologia , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Nefrite Lúpica/patologia , Ativação Linfocitária , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Projetos Piloto , Rituximab , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia
19.
J Invest Dermatol ; 121(1): 81-7, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12839567

RESUMO

Phosphodiesterase inhibitors possess anti-inflammatory and immunomodulatory properties and seem to have a great potential in the treatment of inflammatory skin diseases; however, an overall study on the effects of specific phosphodiesterase inhibitors, such as rolipram on the processes involved in the extravasation of lymphoid cells has not been performed. In this work we have assessed the effect of rolipram on the adhesion, polarization, and migration of normal human T lymphocytes. We found that low concentrations of rolipram were able to inhibit significantly the adhesion of T cells to the beta1 and beta2 integrin ligands vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. Rolipram also interfered with the activation of integrins, and significantly inhibited the homotypic aggregation of T lymphocytes induced by anti-beta1 and anti-alpha4 integrin chain monoclonal antibodies. In addition, rolipram had a downregulatory effect on the activation of T cells, and significantly diminished the expression of the activation antigens CD69, CD25, and CD98 induced by phytohemagglutinin. Finally, this drug inhibited the polarization and transendothelial migration of T lymphocytes induced by the chemokine CXCL12 (SDF-1) and the chemotactic cytokine interleukin-15. The results indicate that rolipram, at low concentrations, exerts an important anti-inflammatory and immunomodulatory effect, and suggest that this selective phosphodiesterase inhibitor may be an effective tool for the therapy of immune-mediated diseases.


Assuntos
Movimento Celular/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Rolipram/farmacologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , 3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Antígenos CD18/metabolismo , Adesão Celular/efeitos dos fármacos , Adesão Celular/imunologia , Agregação Celular/efeitos dos fármacos , Agregação Celular/imunologia , Movimento Celular/imunologia , Polaridade Celular/efeitos dos fármacos , Polaridade Celular/imunologia , Quimiocina CXCL12 , Quimiocinas CXC/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Relação Dose-Resposta a Droga , Endotélio/citologia , Humanos , Técnicas In Vitro , Integrina beta1/metabolismo , Interleucina-15/farmacologia , Ligantes , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/enzimologia
20.
Pediatr Allergy Immunol ; 13(5): 319-27, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12431190

RESUMO

The aim of this study was to identify a novel immunological indicator useful for the early diagnosis (through a rapid and single determination) of neonatal sepsis (NS). Peripheral blood samples were taken from 63 neonates, who were classified into four groups: proven NS (n = 17); clinical NS (n = 14); disease without infection (n = 17); and healthy newborns (n = 15). Neutrophil expression of CD64, CD43, CD44, CD50, CD62L and Mac-1, and plasma levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha) and soluble L-selectin (sCD62L), were determined. Expression of CD64 was significantly enhanced in the group with proven sepsis and clinical NS compared to newborns without infection (p < 0.05). Eight newborns with proven or clinical sepsis, but only one with disease without infection, showed an increased percentage of CD64+ cells (diagnostic specificity = 96.8%). No significant differences were found in the expression of the other leucocyte differentiation antigens studied. As previously described, TNF-alpha and IL-6 levels were significantly elevated in newborns with proven or clinical sepsis compared to neonates without infection (p < 0.05). Our results suggest that, through a single determination, the enhanced expression of CD64 is a highly specific indicator of NS, although its diagnostic sensitivity is low (25.8%). In contrast, we found that plasma levels of IL-1beta and sCD62L, as well as the expression of Mac-1, CD43, CD44, CD50, and CD62L, do not appear to be useful for the diagnosis of NS.


Assuntos
Citocinas/biossíntese , Doenças do Recém-Nascido/diagnóstico , Receptores de IgG/biossíntese , Sepse/diagnóstico , Antígenos CD/biossíntese , Antígenos CD/sangue , Biomarcadores/sangue , Citocinas/sangue , Humanos , Bem-Estar do Lactente , Recém-Nascido , Doenças do Recém-Nascido/metabolismo , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/metabolismo , Klebsiella pneumoniae , Glicoproteínas de Membrana , Proteínas de Membrana/biossíntese , México , Neutrófilos/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas , Valor Preditivo dos Testes , Receptores de IgG/sangue , Sensibilidade e Especificidade , Sepse/metabolismo
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