Aerobic training modulates T cell activation in elderly women with knee osteoarthritis

Osteoarthritis of the knee (kOA) is a disease that mainly affects the elderly and can lead to major physical and functional limitations. However, the specific effects of walking, particularly on the immune system, are unknown. Therefore, this study aimed to analyze the effect of 12 weeks of walking (3×/week) on the leukocyte profile and quality of life (QL) of elderly women with kOA. Sixteen women (age: 67±4 years, body mass index: 28.07±4.16 kg/m2) participated in a walking program. The variables were assessed before and after 12 weeks of training with a progressively longer duration (30–55 min) and higher intensity (72–82% of HRmax determined using a graded incremental treadmill test). The QL was assessed using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and blood samples were collected for analysis with a cell counter and the San Fac flow cytometer. Walking training resulted in a 47% enhancement of the self-reported QL (P<0.05) and a 21% increase in the VO2max (P<0.0001) in elderly women with kOA. Furthermore, there was a reduction in CD4+ cells (pre=46.59±7%, post=44.58±9%, P=0.0189) and a higher fluorescence intensity for CD18+CD4+ (pre=45.30±10, post=64.27±33, P=0.0256) and CD18+CD8+ (pre=64.2±27, post=85.02±35, P=0.0130). In conclusion, the walking program stimulated leukocyte production, which may be related to the immunomodulatory effect of exercise. Walking also led to improvements in the QL and physical performance in elderly women with kOA.

Caracterización del infiltrado linfocitario (CD, CD4, CD8, CD45RO y FOXP3) e inestabilidad microsatelital en pacientes con cáncer colorrectal / Lymphocyte infiltration and microsatellite instability in colorectal cancer patients

Background: In colorectal cancer (CRC) patients, lymphocyte infiltration (LI) and microsatellite instability (MSI) have been associated with better prognosis. Aim: To analyze the association between components of LI (CD3/CD4/CD8/CD45R0/FoxP3) and MSI status with metastatic stages in CRC patients. Material and Methods: Prospective study of 109 patients diagnosed with CRC. The expression of CD3, CD4, CD8, CD45R0 and FoxP3 markers, was evaluated by immunohistochemical analysis, and tumors were classified into negative, low and intense expression. The MSI was assessed with seven markers amplified by PCR from normal and tumoral DNA. Tumors were grouped in MSS (stable)/MSI-low and MSI-high. Statistical analysis was performed with Fischer's exact test. Results: 29 percent, 28 percent, 12 percent and 86 percent of tumors exhibits intense expression of CD3+, CD4+, CD8+ and CD45RO+ lymphocytes, respectively. 84 percent of the tumors presented MSS/ MSI-low and 16 percent had MSI-high. Tumors that show a high density of T cells (CD3+, CD4+ y CD45R0+) are associated with early stage tumors (I and II) (p = 0.023; p = 0.030 and p = 0.003, respectively). Additionally, there was a significant association between the MSS/MSI-low tumors and a reduced ability to recruit CD8+ cytotoxic T lymphocytes (p = 0.037) and CD3+ (p = 0.064). Conclusion: There is an association between high densities of CD3+, CD4+ and CD45RO+ lymphocytes and non-metastatic tumors. In addition, MSS/ MSI-low tumors are associated with a lower recruitment of CD8+ and CD3+ lymphocytes.

Introducción: En el cáncer colorrectal (CCR), se sugiere que un mejor pronóstico podría asociarse a una respuesta inmune antitumoral (del huésped) y/o a la presencia de una alta inestabilidad microsatelital (MSI). Objetivo: Determinar si los niveles de expresión de los marcadores de linfocitos T (CD3/CD4/CD8/ CD45RO/FoxP3) y el estado de MSI se asocian a estadios metastásicos en pacientes con CCR. Material y Método: Estudio prospectivo de 109 pacientes con diagnóstico de CCR. El análisis de expresión de los marcadores CD3/CD4/CD8/CD45RO/FoxP3 fue realizado por inmunohistoquímica; los tumores fueron clasificados en negativo, débil e intenso. La MSI fue evaluada con siete marcadores amplificados desde ADN normal y tumoral; los tumores fueron agrupados en: MSS (estable)/MSI-baja y MSI-alta. El análisis estadístico fue realizado con el test exacto de Fischer. Resultados: Una intensa expresión de los marcadores CD3+, CD4+, CD8+ y CD45RO+, fue observada en el 29 por ciento, 28 por ciento, 12 por ciento y 86 por ciento de los tumores, respectivamente. El 16 por ciento de los tumores presentó MSI-alta. Los tumores que presentan una alta densidad de linfocitos T (CD3+, CD4+ y CD45RO+) se asocian a estadios tempranos I-II (p = 0,023; p = 0,030 y p = 0,003, respectivamente). Adicionalmente, se identificó una asociación estadística significativa entre los tumores con MSS/MSI-baja y una menor capacidad de reclutar linfocitos T citotóxicos CD8+ (p = 0,037) y totales CD3+ (p = 0,064). Conclusión: Existe una asociación entre altas densidades de linfocitos T CD3+, CD4+ y CD45RO+ y tumores con estadios no metastásicos. Además, tumores con MSS/MSI-baja se asocian a un menor reclutamiento de linfocitos T CD8+ y CD3+.

Recuento absoluto de linfocitos como factor predictivo en el trasplante hematopoyético / Absolute lymphocyte count as a predictor in hematopoietic transplantation

La recuperación temprana de linfocitos es un factor pronóstico que está relacionado con una mayor supervivencia libre de eventos y supervivencia global en pacientes trasplantados. Se realizó una revisión bibliográfica con el objetivo de determinar el valor pronóstico del recuento absoluto de linfocitos en pacientes con hemopatías malignas, tratados con trasplante. Los pacientes con trasplantes autólogos alcanzan un recuento absoluto de linfocitos el día + 15 (RAL15) e 500 x mm³, más temprano que los alogénicos. El RAL15 cuando se utiliza sangre periférica es mayor que cuando se emplea la médula ósea. Los factores pronósticos asociados a una peor supervivencia global fueron la sepsis, el RAL15 < 500x mm³ y la recaída. Varios estudios muestran una mejor supervivencia global y supervivencia libre de eventos a los cinco años, en los pacientes con RAL15 e 500 x mm³. El RAL15 e 500 x mm³ es una herramienta simple y útil para predecir un mejor resultado en pacientes sometidos a trasplante hematopoyético

Early recovery of lymphocytes is a prognostic factor that is related to a higher event-free survival and overall survival after haematopoietic stem cell transplantation. A literature review was conducted in order to determine the prognostic value of absolute lymphocyte count in patients with hematological malignancies after transplantation. Autologous transplant patients reach an absolute lymphocyte count on day + 15 (RAL15) e 500 x mm³, earlier than allogeneic. The RAL15 when peripheral blood is used is greater than when using the bone marrow. Prognostic factors associated with worse overall survival were sepsis, RAL 15 <500x mm³ and relapse. Several studies show a better overall survival and event-free survival at five years in patients with e 500 x RAL15 mm³. The RAL15 e 500 x mm³ is a simple and useful tool to predict a better outcome in patients undergoing hematopoietic transplantation

A novel noninvasive method to detect rejection after heart transplantation

Prompt and accurate detection of rejection prior to pathological changes after organ transplantation is vital for monitoring rejections. Although biopsy remains the current gold standard for rejection diagnosis, it is an invasive method and cannot be repeated daily. Thus, noninvasive monitoring methods are needed. In this study, by introducing an IL-2 neutralizing monoclonal antibody (IL-2 N-mAb) and immunosuppressants into the culture with the presence of specific stimulators and activated lymphocytes, an activated lymphocyte-specific assay (ALSA) system was established to detect the specific activated lymphocytes. This assay demonstrated that the suppression in the ALSA test was closely related to the existence of specific activated lymphocytes. The ALSA test was applied to 47 heart graft recipients and the proliferation of activated lymphocytes from all rejection recipients proven by endomyocardial biopsies was found to be inhibited by spleen cells from the corresponding donors, suggesting that this suppression could reflect the existence of activated lymphocytes against donor antigens, and thus the rejection of a heart graft. The sensitivity of the ALSA test in these 47 heart graft recipients was 100%; however, the specificity was only 37.5%. It was also demonstrated that IL-2 N-mAb was indispensible, and the proper culture time courses and concentrations of stimulators were essential for the ALSA test. This preliminary study with 47 grafts revealed that the ALSA test was a promising noninvasive tool, which could be used in vitro to assist with the diagnosis of rejection post-heart transplantation.

Humoral and cellular immune responses as diagnostic tools in human toxoplasmosis

The study was conducted to assess the humoral and cellular immune responses in patients suspected to have Toxoplasma infection, and to evaluate their use as diagnostic tools. Seventy six persons were enrolled in the study, 56 of them are patients with toxoplasmosis. In addition to 20 apparently healthy persons were served as control. They were divided into 4 main groups according to their signs and symptoms, Group I, 17 patients with ocular signs and symptoms suggestive of toxoplasmosis Group II, 23 patients complaining of complicated obstetric problems, Group III, 9 infants and children with signs and symptoms of congenital toxoplasmosis, and Group IV, 7 patients with manifestations suggesting toxoplasmic lymphadenopathy. RH Toxoplasma strain was used. Experimental animals: 400 mice were used, 10 each time, for maintainance of Toxoplasma strain, by regular serial passage and for preparation of antigen. Enzyme linked immunosorbent assay [ELISA] for detection of anti Toxoplasma IgG and IgM antibodies. Lymphocyte transformation test were done for detection of specific lymphocyte proliferation [blastogenic response]. Out of total 56 patients, 49 patients [87.5%] gave positive results to Toxopasma antigen in one or more of the specific techniques applied. Seven patients gave negative results were recommended for periodic follow up before exclusion of toxoplasmosis. High rates of seropositivity detected among suspected patients suggest the reliability of ELISA in diagnosis of toxoplasmosis. Specific lymphoblastognic response would confirm the results and reveal dormant infection in some suspected subjects. However, rising titre/ seroconversion is a prerequisite for therapy

Actividad supresora del millerenólido sobre células mononucleares de sangre periférica humana / Millerenolide induces suppressive activity on human peripheral blood mononuclear cells

Background: Natural products are used in the production of therapeutic drugs due to their wide diversity and excellent adaptability to biological structures. Sesquiterpene ¡aciones are the active constituents of several plants from the Asteraceae family. Aim: To assess the in vitro effect of a sesquiterpene lactone (millerenolide). Material and methods: The drug effect was assessed measuring the proliferation of lymphocytes using the 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonylJ-2H-tetrazolium hydroxide (XTT) technique. Changes on the cell cycle were analyzed on a FACSort flow cytometer The effect of millerenolide on the production of nitric oxide (NO) by macrophages was evaluated using the Griess reagent. Additionally, phagocytosis of latex particles and nitroblue tetrazolium (NBT) reduction by macrophages were evaluated microscopically. Results: Treatment of human peripheral blood mononuclear cells (PBMC) with millerenolide decreases the proliferation of lymphocytes, decreases the percentage of cells in S, and G2/Mphases, and increases the proportion of cells in GO/Gl phase. Treatment of macrophages with millerenolide, reduces the production of NO, the phagocytic capacity and the number of cells able to reduce NBT. Cytotoxic effects of the lactone on human PBMC were only observed when the concentration was increased to 6 fig/ml. Conclusions: Millerenolide could be considered as a potential therapeutic agent with immunosuppressiveproperties.

Células dendríticas como determinantes del equilibrio entre inmunidad y autoinmunidad / Dendritic cells like determinants of the balance between immunity and autoimmunity

Autoinmune diseases occur when the immunological system loses its capability to recognize between self and foreign, and develops a response against healthy tissues. Both molecular bases that trigger these pathologies and genetic factors of susceptibility are unknown. Identification of these factors is fundamental for understanding and developing specific therapies for autoimmune diseases. Dendritic cells (DCs) - professional antigen presenting cells - play a fundamental roll in the development and modulation of the acquired immune response because they have the unique capacity to active naïve T lymphocytes. In order to activate T lymphocytes, the DCs must supply simultaneously two molecular signals which correspond to the antigen (or peptid complex MHC) plus costimulating signals. In absence of costimulation, the DCs induce inactivation of T lymphocytes, mechanism by which they are able to maintain peripheral tolerance against self antigens. In this way, it has been proposed that the immature DCs present antigens in absence of costimulation and provoke tolerance. On the contrary, mature DCs present antigens together with costimulating signals, which lead to immunity. In self-immune diseases, the process of tolerance in the presence of autoantigens could be deficient due to alterations in the normal function of DCs. One of the causes of this defect could be that there is an unbalance in the expression of activating and inhibiting Fcy receptors on the surface of DCs. This would generate DCs with a constitutive phenotype of maturity that would interfere with its tolerogenic activity, and would favor the permanent activation of T lymphocytes, including those that are autoreactive.

Prolactina como inmunomodulador / Prolactin how immunomodulator

El propósito de la presente revisión es explorar el papel de la prolactina como inmunomodulador en la respuesta inmune. La prolactina tiene función trófica en la proliferación de los linfocitos. Las células del sistema inmunitario tienen receptores en su superficie para la prolactina, más aún, los linfocitos son capaces de sintetizar y secretar prolactina. Diferentes estados en el nivel de prolactina ejercen una respuesta diferente en el sistema inmunitario, la disminución en la prolactina provoca un deterioro en la respuesta inmunitaria, mientras que el aumento de la prolactina ejerce un incremento de la respuesta inmunitaria. Las alteraciones en la prolactina se han descrito en muchas enfermedades con fondo inmunológico, como el lupus eritematoso sistémico, el síndrome de Reiter, artritis por adyuvantes, uveítis, transplante de órganos. La acumulación de pruebas al momento actual del papel que juega la prolactina como inmunomodulador puede tener un profundo impacto clínico en las enfermedades autoinmunitarias pero aún están en camino de determinarse

Stressful stimulation of newborn mice increases the in vitro proliferative response in T cells from thymus

The effects of prolonged stressful stimulaton on the in vitro proliferative response of thymic T cells and the thymic zinc concentration were investigated in newborn Balb/c mice. Animals were stressed y intraperitoneal injections with aliquots from a heat-killed staphyloccocal suspension over one month. The splenic T lymphocytes from the stressed animals showed a significant reduction in the in vitro response to cancanavalin A (Con-A) stimulation. However, an unexpected and significant increase in proliferative response was observed when thymic lymphocytes from stressed animals were stimulated with the same mitogen. The intrathymic zinc levels were regularly elevated in stressed mice, in contrast to those values obtained in the thymus from healthy control mice. These results suggest that neonatal stress can disrupt the intrathymic maturation and the selection of pre-T lymphocytes. The increment of the in vitro proliferative response of T cells from of thymus of stressed mice may be caused by proportionally higher amounts of intrathymic lymphoid suppopulations expressing a mature phenotype and functionality

Influencia de las condiciones de cultivo de placenta humana sobre la producción de medios condicionados placentarios / Influence of culture conditions on the production of human placent conditioned medium

En este trabajo se propone una técnica alternativa para la obtención de medios condicionados derivados de placenta humana. Se cultivaron homogenatos placentarios en Mc Coy's 5A suplementado con suero fetla bovino al 5 por ciento y 25mM de HEPES a 37oC. Luego de seis días, los cultivos fueron sacrificados, verificándose la esterilidad y la viabilidad celular. El sobrenadante fue centrifugado a 22.000 g 30 min a 4oC y esterilizado por filtración (0,22 um), denominándolo Medio Condicionado de Placenta Humana (MCPH). Se probó la actividad de los extractos, así obtenidos, en cultivos de linfocitos periféricos de mujeres con tres hijos, con la adición de MCPH al 5 por ciento ,10 por ciento y 20 por ciento y se determinó el índice de Transformación Blástica Linfocitaria (ITBL). La máxima estimulación se observó en los cultivos linfocitarios que contenían MCPH al 10 por ciento , siendo estos valores más uniformes que losa producidos con MCPH al 10 por ciento obtenidos por otra técnica. en conclusión, con esta metodología es posible obtener medios condicionados placentarios con una actividad estimulante más uniforme, independientemente de la placenta de la cual provengan

Niveles de Beta-2 microglobulina en pacientes mexicanos con SIDA: asociación con la gravedad del padecimiento / Levels of Beta-2 microglobulin in mexican patientes with aids: association with the severity of the disease

El objetivo del presente trabajo fue analizar niveles de beta-2 microglobulina (ß2MG) en pacientes mexicanos con SIDA y determinar si éstos tenían asocición con la gravedad del padecimiento. Utilizando radioinmunoanálisis, se midió la ß2MG durante la evaluación inicial de 29 pacientes con SIDA referidos al Instituto Nacional de Cancerología. Dieciocho pacientes tenían sarcoma de Kaposi, siete infección oportunista y cuatro linfoma no-Hodgkin de alto grado. De los 18 sujetos con carcoma de Kaposi, 10 tuvieron enfermedad agresiva que requirió de tratamiento. en todos estos caso el nivel de ß2MG fue de 3.5 a 8.0 mg/l (promedio de 4.54). Los otros ocho pacientes con sarcoma de Kaposi tenían enfermedad indolente, y sus niveles de ß2MG fueron menores a 3.5 mg/l (promedio de 1.97). La diferencia entre las medias fue estadísticamente significativa (p < 0.001). los pacientes con infecciones oportunistas presentaron niveles de 1.42 a 5 mg/l (promedio de 3.41). Los niveles no correlacionaron con las supervivencia, el tipo de infección o las cuentas de linfocitos CD4. En los cuatro pacientes con linfoma, los niveles de ß2MG variaron de 1.66 a 3.24 mg/l (promedio de 2.26) y no correlacionaron con la etapa clínica o la supervivencia. por otra parte, los niveles de ß2MG se encontraron elevados (> 4.9 mg/l) en los tres pacintes con síndrome de desgaste. Nuestros datos sugieren que los pacientes con sarcoma de Kaposi y niveles de ß2MG superiores a 3.5 mg/l tienen enfermedad agresiva que requiere de tratamiento. Asimismo, los niveles más altos de ß2MG se asociaron a síndrome de desgaste grave