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Acquired aplastic anemia(AA) is a disease of bone marrow failure mediated by autoimmune T cells. CD4+CD25+ regulatory T cells, which have immunosuppressive and anergic, belong to a subpopulation of T cells specialized for immune regulation and play important roles in the development of autoimmune T cells. Foxp3 plays a significant role in the development and function of regulatory T cells which have been confirmed by many investigations. In recent years, the relationship between CD4 +CD25 +Foxp3 + regulatory T cells and AA has become a hot spot of research. What’s more, its clinical significance is becoming more and more obvious in AA.
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Objective To evaluate the immunogenicity and immunoprotective effect of heat shock protein 60 kDa (SjHSP60) of Schistosoma japonicum in mice after immunization and challenge infection, and explore the mechanism. Methods B cell/an?tibody?related databases and analysis tools were used to predict B?cell epitopes of SjHSP60. The mice were immunized with the recombinant SjHSP60 and challenged with S. japonicum cercariae. SjHSP60?specific antibodies in serum were detected by ELI?SA. The level of splenocyte proliferation was determined by 3H?TdR incorporation. Ex vivo suppression assay was performed to in?vestigate the effects of CD4 +CD25 + regulatory T cells (Tregs) induced by SjHSP60. Results SjHSP60 possessed multiple pre?dominant regions of B?cell epitopes. SjHSP60 induced a significant increase in both SjHSP60?specific IgG levels (P 0.05) and liver?accumulated eggs (P > 0.05) in S. japonicum?infected mice. Ex vivo assay showed that CD4+CD25+ Tregs from SjHSP60?immunized mice enhanced immunosuppressive activity. Conclusion SjH?SP60 has a dual role in host immune system, being involved in the induction of dominant humoral and cellular immune responses as well as in the enhancement of immunosuppression.
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@#BACKGROUND: Sepsis is a common complication of infections, burns, traumas, surgeries, poisonings, and post-cardiopulmonary resuscitation. The present study aimed to investigate prognostic value of CD4+CD25+ regulatory T cells (Treg) in peripheral blood of patients with sepsis. METHODS: Periphery blood from 28 patients diagnosed with sepsis was collected on day 1 and 7 after hospitalization in the ICU of Shanghai Changzheng Hospital between December 2013 to April 2014. The blood was used for analyses of Treg ratio using flow cytometry and for analyses of blood routine test, C-reactive protein (CRP), bilirubin, procalcitonin (PCT), and coagulation. APACHE II and sequential organ failure assessment (SOFA) scores were also investigated. The results were compared between two outcome groups of survival or death to evaluate prognostic value for sepsis. RESULTS: The patients had an average age of 60.36±15.03 years, APACHE II score 16.68±7.00, and SOFA score 7.18±3.78. Among the 28 patients, 12 had severe trauma (42.9％), 10 had septic shock (35.7％), and 9 (32.2％) died. The median ratio of Tregs was 2.10％ (0.80％, 3.10％) in the survival group vs. 1.80％ (1.15％, 3.65％) in the death group (Z=–0.148, P=0.883) on day 1; however it was significantly changed to 0.90％ (0.30％, 2.80％) vs. 5.70％ (2.60％, 8.30％) (Z=–2.905, P=0.004). CONCLUSION: With better prospects for clinical application, dynamic monitoring of Tregs ratio in peripheral blood has potential value in predicting prognosis of sepsis.
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Objective To investigate the effects of wet hyperthermia combined with microwave ablation on the pro-portion and function of CD 4 +CD25 +regulatory T cell in animal model of mouse mammary carcinoma and explore its significance .Methods An experimental model of mouse mammary carcinoma was established and then treated with microwave ablation on day 14.Local wet hyperthermia was also performed .The proportion of CD4 +CD25 +regula-tory T cells (Tregs) in splenocytes was analyzed by FACS.The relative expression of Foxp3, as well as the expres-sion of CTLA-4 and GITR, on Tregs was determined by real-time PCR assay and FACS respectively .Moreover, the secretion of TGF-βand IL-10 from Tregs also were detected by ELISA .In addition , the suppressive capacity of Tregs on CD4 +CD25 -T cell was also examined by MTT assay .Results The proportion of Tregs in wet hyperther-mia combined with microwave ablation treated group decreased significantly compared with that in wet hyperthermia or microwave ablation treated alone group ( P<0.05 ) .Moreover , the expression level of Foxp 3 on Tregs decreased significantly (P<0.05).Furthermore, the expression of CTLA4 and GITR, as well as the secretion of TGF-βand IL-10, on Tregs also obviously decreased (P<0.05).Finally, the suppressive capacity of Tregs on the proliferation of CD4+CD25-T cells were also significantly impaired ( P<0.05) .Conclusions Wet hyperthermia combined with microwave ablation os more effective than single wet hyperthermia or microwave ablation as a mono -therapy alone on the function of Tregs , which may be closely related to the enhanced suppression of tumor growth .
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Objective:To investigate the changes of the levels of CD 4+CD25+Foxp3+regulatory T cells in HDCP peripheral blood and its significance.Methods: From 2013 January to 2014 August 46 hypertensive disorder complicating pregnancy ( HDCP ) patients treated in our hospital ,including 22 patients with mild preeclampsia ,24 cases of severe preeclampsia ,and 25 normal pregnant women,used flow cytometry detected each group patient peripheral blood CD 4+CD25+Foxp3+regulatory T cells.Results: Severe preeclampsia group CD4+CD25+T cell ratio was (5.01±1.04)%,lower than mild preeclampsia group (7.38±1.26)% and normal pregnant women group ( 12.59 ±2.48 )%, the difference was statistically significant ( P<0.05 );Mild preeclampsia and severe preeclampsia group CD4+CD25+Foxp3+T cell absolute number respectively were (0.96±0.11) ×107 and (0.63±0.12) ×107,CD4+CD25+Foxp3+Treg/CD4+T were (2.58±0.93)%and (1.84±0.85)%,were lower than that of normal pregnant women group (1.85± 0.17) ×107 and(5.11±0.99)%,the difference was statistically significant (P<0.05);Mild preeclampsia group and severe preeclampsia blood estriol were (6.16±2.17) mg/L and (3.27±1.15) mg/L,significantly lower than that of normal pregnant women group (11.34±2.4) mg/L,the difference was statistically significant (P<0.05).Conclusion: Hypertensive disorder complicating pregnancy diseases patient CD 4+CD25+Foxp3+regulatory T cells was significantly reduced ,but also serum estriol reduced ,which may be related to the pathogenesis of gestational hypertension disease and immune tolerance .
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Objective:To discuss the changes and significance of CD4+CD25+regulatory T cells and cytokines in patients with rheumatic heart disease compared to the normal people.Methods:Clinical data of patients with RHD received treatment at our hospital from April 2012 to July 2010 was retrospectively analyzed.The normal control group was the healthy physical examination persons form the medical examination center at our hospital.The expression levels of growth factorβ1 (TGF-β1),tumor necrosis factor alpha (TNF-α),interleukin-10 (IL-10),interleukin-6 (IL-6) and CD4+CD25+regulatory T cells in the peripheral blood samples of the objects in the two groups were detected and compared.Results:A total of 76 patients were retrospective analyzed,including 40 in observe group and 60 in control group.The percent of CD4+CD25+T accounted for lymphocyte and the percent of CD4+CD25+Foxp3+Treg accounted for CD4+T in observe group were obviously lower than those in control group.The TGF-β1 and IL-10 in observe group were obviously lower than those in control group.The TNF-αand IL-6 in observe group were obviously higher than those in control group.The differences had statistical significance.Conclusion: The CD4+CD25+ regulatory T cells in patients with RHD were obviously decreased.The blood cytokines such as TGF-β1 and IL-10 were corresponding declined.
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CD4 + CD25 + regulatory T cells are produced in the thymus and have anergic and immunosuppressive properties.Researchers measured the antibody level related with CD4+ CD25+ T cells,CD4+ CD25hi T cells,CD4+ CD25+ Foxp3 and CD4+ CD127 in regenerative anemia,leukemia,ITP,NHL,MDS.Then they got the conclusions that regulatory T cells decreased in the autoimmune blood diseases and increased in the neoplastic diseases.The regulatory T cells have great prospect in the treatment of autoimmune diseases,allergic diseases,transplant rejection,tumors and specific vaccination.
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Lymphocyte subsets in peripheral blood and function of CD4+CD25+ regulatory T cells(Tregs) were assayed in patients during different periods of Graves' disease ( GD ).Breakdown of Tregs' function lead to the wild proliferation of CD4+T lymphocyte,and may play an important role in the pathogenesis of GD.It is difficult to fully restore the Tregs' function to normal after successful medication in Graves' disease,this phenomenon may lead to easy relapse of GD.
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Objective: To investigate the association between deficiencies of early components in the classical complement pathway and the development of SLE. Methods: Forty inbred C57BL/6J mice and 40 knockout C4 complement gene (C4KO) mice, which included 10 mice in each age group (2, 4, 6, and 8 months) were used. The enumeration of CD4+CD25+ Tregs frequencies in bone marrow, spleen and peripheral blood from both normal and C4KO groups were performed by flow cytometry. The expression levels of Foxp3 and TGF-b in the same tested tissues were measured using real time PCR. The antinuclear antibodies (ANA) were semi-quantitatively measured using ELISA. Results: We report decreased frequencies of CD4+CD25+ Tregs and reduced expression levels of Foxp3 and TGF-β, which efficiently program the development and function of Tregs, in lymphoid tissues and peripheral blood of C4KO mice. In this study, C4KO mice have higher titers of ANA than those of normal mice. Higher frequencies of mice positive for ANA are also found in older mice.Conclusions: The deficiency of the C4 gene induces the decreased numbers of Tregs that further increase the production of ANA resulting in the development of an autoimmune disorder. The outcomes of our study help us to understand the association between the deficiency of C4 in the classical complement pathway and development of autoimmune disorder via the role of Tregs.
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Objective To examine the contribution of CD4+ CD25+ regulatory T cells to liver transplant tolerance. Methods After injection of anti-CD25 monoclonal antibody (mAb, PC61), mouse orthotopic liver transplantation was performed and survivals were determined. The paraffin-embedded sections of hepatic allografts were cut and stained with hematoxylin and eosin (HE). Furthermore, the effect of CD4+ CD25+ regulatory T cells on proliferative response of CD4+ T cells and cytotoxicity of CD8+ T cells was examined by depleting these regulatory T cells. Results Depletion of these cells in the recipients but not in the donors before liver transplantation caused rejection. Histological analyses of hepatic allografts with PC61 treatment showed extensive leukocyte infiltration and tissue destruction, whereas those in the control group showed minimal changes. Moreover, elimination of CD4+CD25+ T cells resulted in the enhancement of both proliferative response of CD4+ T cells and cytotoxicity of CD8+ T cells against donor-type alloantigen. Conclusions These results suggest that CD4+CD25+ regulatory T cells were important for tolerance induction to hepatic allografts.
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ObjectiveTo investigate the effect and related mechanism of triptolide pretreatment to prevent from ischemia/reperfusion (I/R) injury in mice liver. MethodsSixty male C57BL/6 mouse were randomized into four groups (15/group): A:sham group with saline , B: sham group with triptolide, C: saline I/R group, D: triptolide I/R group. The mice were pretreated with either saline or triptolide (0. 1 mg/kg/d) through intraperitoneal (ip) injection for one week. The mouse partial liver model of I/R injury was established, and samples were collected at 24 h after the I/R injury. ResultsSerum ALT and AST levels were significantly decreased and histological damage was significantly alleviated in the triptolide I/R group as compared with the saline I/R group (P＜0.05), the concentration of MDA in the triptolide groups was significantly decreased, while SOD activity was significantly increased compared with that of the saline I/R group (P＜0.05). The percentages of CD4+ CD25+ regulatory T cells (Tregs) cells among CD4+ T cells in groups A, B, C, and D were(7. 55 ± 1.87)%, (12. 59±3. 87)%,(7. 85±1.07)%, and(12. 02±3. 16)% in liver tissue, respectively. The expression levels of Foxp3 mRNA were significantly higher in the triptolide I/R group than those of saline I/R group (P＜0. 05). ELISA showed that triptolide could significantly inhibit the levels of IL-6, IL-Iβ and TNF-αand promoted the level of IL-10 in the serum (P＜0.05). Conclusion Pretreatment with triptolide could effectively prevent from liver I/R injury, which may be related to the induction of Treg cells by triptolide, the increase in the level of IL-10 in serum, and the inhibition of IL-6, IL-1β and TNF-α production in serum.
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Introducción: El Herpes Labial Recurrente supone una condición inmunológica alterada, tal como una hiperactividad de células T-reguladoras CD4+CD25+ (Treg). Éstas ejercen control sobre la tolerancia periférica y reducen el riesgo inmunopatológico, suprimiendo otras líneas celulares. Por ende, la supresión ejercida sobre la reacción inmune antiviral podría afectar negativamente el curso de la infección. Este contexto ha impulsado la búsqueda de nuevas alternativas inmunomoduladoras como la Equinácea purpúrea. Dada su propiedad inmunosupresora, se propone en el tratamiento del Herpes Labial Recurrente. Metodología: Estudio clínico prospectivo que analiza las subpoblaciones linfocitarias en 12 pacientes con Herpes Labial Recurrente, antes y después de recibir Equinácea purpúrea (30 gotas tres veces al día durante siete días).Resultados: En comparación con individuos sanos, los pacientes presentan una respuesta aumentada de células Treg. Esta condición se reduce significativamente tras recibir Equinácea purpúrea (515 + 145 y 432 + 113 cel/mm3 antes y después del tratamiento, respectivamente, p < 0,005). Conclusión: La hiperactividad de células Treg podría explicar el estado de inmunosupresión de estos pacientes y favorecería la persistencia viral. Se propone esta fitomedicina como una alternativa inmunoterapéutica beneficiosa.
Background: Recurrent Herpes Labialis patients may suffer from immunological alterations, such as CD4+CD25+Regulatory-T Cell (Treg) hyperactivity. These cells control peripheral tolerance and reduce immunopathology risk by suppressing other immunological cells. Hence, the Treg cell suppression on the antiviral immune reaction may perturb adversely the herpes infection outcome. This scenario has forced physicians to explore new immunomodulatory alternatives in Phytomedicine, such as Echinacea purpurea. Regarding the immunosuppressive property, it has been challenged to be employed in the Recurrent Herpes Labialis management. Methods: Clinical prospective study that analyzed lymphocytic subpopulation profile in twelve patients with Recurrent Herpes Labialis, before and after receiving E. purpurea (30 drops three times a day during seven days). Results: Comparing to healthy subjects, patients presented an enlarged Treg cell response. This condition became significantly reduced after receiving E. purpurea. (515 + 145 and 432 + 113 cel, before and after treatment respectively, p < 0.005). Conclusion: The intensified Treg cell activity may elucidate the immune suppression these patients undergo, aiding the viral persistence and survival. This proposes E. purpurea asa beneficial immunotherapeutic alternative.
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Humans , Antiviral Agents/therapeutic use , Echinacea/therapeutic use , Echinacea/chemistry , Herpes Labialis/drug therapy , Plant Preparations/therapeutic use , Antiviral Agents/pharmacology , Echinacea/pharmacology , Herpes Labialis/immunology , Herpes Simplex/drug therapy , Herpesvirus 1, Human , Immunomodulation , Multicenter Studies as Topic , Prospective Studies , Plant Preparations/pharmacology , Recurrence/prevention & control , T-Lymphocytes, RegulatoryABSTRACT
CD+4 CD+25 regulatory T cell (Treg) has immune incompetent and immune suppression functions, and is a kind of suppressor T-cell subsets. It can inhibit the activation and proliferation of CD+4 T cells and CD+8 T cells, so as to effectively suppress the immune system to foreign organ and reduce the graftversus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT), without affecting the role of graft-versus-leukemia (GVL), which plays an important role in the transplantation immune tolerance.
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AIM: To investigate the effect of glucocorticoid inhalation on the levels of CD4~+CD25~+ regulatory T cells in peripheral blood of asthmatic children. METHODS: Glucocorticoid inhalator was inhaled by 70 children with attack asthma. The levels of CD4~+CD25~+ Tr in peripheral blood of asthmatic children were tested by flow cytometry (FCM). RESULTS: The CD4~+CD25~+ Tr levels in peripheral blood of asthmatic children were (5.62% ± 1.29% ) and (7.05% ± 1.61%) before and after of regulated glucocorticoid inhalation, respectively (P<0.01). The Tr levels were (7.56% ± 1.88% ) , (7.09% ± 1.23% ) and (6.11% ± 1.96% ) in the complete control group, part control group and poor control group, respectively ( P < 0.05 ). The Tr level in formal treatment group (7.05% ±1.61%) was higher than that in irregular treatment group ( 5.91 % ± 1.76% ), P < 0.01.CONCLUSION: The level of CD4~+CD25~+ Tr is remarkable increased by regulated glucocorticoid inhalation, and the level of Tr can reflect the effects of glucocorticoid inhalation.
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To know CD+4 CD+25 regulatory T cells' s function in tumor immunological regulation and to search for its functionary molecule mechanism by reviewing researches associated with the characteristics of CD+4 CD+25 regulatory T cells surface molecules and the expression of CD+4 CD+25 regulatory T cells in the peripheral blood and tissues.
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Objective To investigate the proportion of CD_4~+ CD_(25)~+ Tregs in the peripheral blood of the patients suffering from acute myeloid leukemia (AML) with or without chemotherapy and clinical significance.Methods The flow cytometry was used to evaluate the proportion of CD_4~+ CD_(25)~+ CD_(127)~(low) T cells in the peripheral blood of the patients with primary AML group (group A), AML who achieved complete remission over 3 years (group C) or less than 3 years(group B) and the healthy donors. Results The percentages of CD_4~+ CD_(25)~+ Tregs of group A and B was significantly higher than that of control group (P 0.05). The percentages of CD_4~+ CD_(25)~+ Tregs of group A was significantly higher than that of group B and C. Conclusion These results suggested that CD_4~+ CD_(25)~+ Tregs played an important role in acute myeloid leukemia.
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Objective To evaluate the alteration of CD4+ regulatory T cells in peripheral blood from patients with ankylosing spondylitis(AS). Methods Seventy-eight AS patients and 50 healthy individuals were included in this study. The proportion of CD4+CD25+CD127lo/- T cell population in CD4+ T cells as well as that cytotoxic T lymphocytes(CTL) and NK cells in lymphocytes was evaluated by flow cytometry. Serum TGF-β and TNF-α were measured by ELISA. The inhibitory function of CD4+CD25+ regulatory T cells was measured by mixed lymphocyte culture. Results The population of CD4+CD25+CD127lo/- T cells in peripheral blood of AS patients accounted for (4.36±1.21)% of CD4+ T lymphocytes, which was significantly lower than that in healthy individuals (P<0.05). The CD4+CD25+CD127lo/- T cells population in AS patients was positively correlated with TGF-β level, but negatively with TNF-α. Compared with healthy individuals, the function of CD4+CD25+ regulatory T cells in the inhibition of alloreactive T cells was lower in AS patients, which was related to the decreased secretion of TGF-β. Conclusion The CD4+ regulatory T cells in peripheral blood of AS patients are significantly decreased and its function is defective, which leads to immune regulatory dysfunction in vivo. It may be one of immune pathogenesis mechanisms of AS.
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The changes of CD4+CD25+ regulatory T cells (CD4+CD25+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible roles of CD4+CD25+ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls (normal control group) and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4+CD25+ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4+CD25+ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups (P＜0.05). Although the CD4+CD25+ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them (P＞0.05). As compared with persistent group, exacerbation group had lower CD4+CD25+ Treg ratio and Foxp3 mRNA (P＜0.05). It was indicated that the decrease of CD4+CD25+Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.
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[Objective] To investigate the changes of CD4+CD25+Foxp3+regulatory T cells (Tregs) in peripheral blood of patients with esophageal carcinoma and its possible clinical significance.[Methods] The flow cytometry was used to evaluate the population of CD4+,CD25+,Foxp3+T cells in the peripheral blood of the patients with esophageal carcinoma before therapy and of the healthy donors.[Results] The percentage of CD4+,CD25+,Foxp3+T cells of the esophageal carcinoma group before therapy was significantly higher than the healthy donors group (P
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Objective To investigate changes of CD~+_4CD~+_ 25 regulatory T cells (CD~+_4CD~+_ 25 Treg) and forkhead/winged helix transcription factor(Foxp3) mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma, so as to elucidate the possible roles of CD~+_4CD~+_ 25 Treg in the development of asthma. Methods The peripheral blood samples were collected from 29 healthy controls (normal control group) and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD~+_4CD~+_ 25 Treg ratio and Foxp3 mRNA in PBMCs were detected. Results The CD~+_4CD~+_ 25 Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent group were lower than that of remission group and normal control group (P0.05). Compared with persistent group, exacerbation group had lower CD~+_4CD~+_ 25 Treg ratio and Foxp3 mRNA (P