Alterações induzidas pelo estresse crônico de contenção na diferenciação de linfócitos T em camundongos Balb/c

Abstract

Studies have confirmed the hypothesis that stress alters immune function and can influence the development of autoimmune diseases, infectious diseases, cancer and AIDS. In experimental models, stress alters the number of circulating lymphocytes, the production of inflammatory cytokines and antibodies secretion and the lymphocyte migration to skin and mucosa. The purpose of this study was to analyse the alterations induced by chronic restraint stress in BALB/c mice T-celldifferentiation. As expected, chronic restraint stress carried increase ofcorticosterone levels, showing the efficacy of the stress protocol used. Six-week-old BALB/c mice were maintained under restraint during 5 consecutive days, 2 hours per day. At day 6 of stress, the animals were sacrificed and the thymus was collected for histological analysis and immunophenotyping of thymocytes. Chronic restraint stress induced thymus involution, mainly of cortical region, thymus weight decrease andcellularity reduction of this organ. By using triple staining of surface proteins in thymocytes and flow cytometry analysis, it was demonstrated that stress induced increase in the frequency of CD3- cells and decrease of CD3+ thymocytes. The analyzis of CD3- thymocytes showed an increase in the frequency of pro-T1 (CD44+CD25-) and pro-T2 (CD44+CD25+) subsets and decrease of pro-T3 (CD44- CD25+) and pro-T4 (CD44-CD25-). These data suggest that chronic restraint stresscompromises thymocyte differentiation, mainly in the stage from pro-T2 to pro-T3. The analysis of CD3+ thymocytes revealed decreased frequency of CD3+CD4-CD8- subset and increased frequency of CD3+CD4+CD8+ subset. Chemical sympathectomy with 6-OH dopamine did not inhibited thymic involution, showing that norepinefrine does not act, significantly, in this process. Spleen triple staining of lymphocytes and flow cytometry analysis showed immature T lymphocyte and decrease of CD3+CD4+CD8- subset. The data presented here demonstrated that thealterations in the thymocytes differentiation induced by chronic restraint stress have a systemic involvement and can compromise peripheral immune system carrying out diseases development.