THE ROLE OF REGULATORY T CELLS IN FRAILTY IN MEN WHO HAVE SEX WITH MEN

HIV infection;frailty;regulatory T cells;immune activation;immunosenescence;immune exhaustion;MACS;frailty phenotype;Immunology

Zhang, WeiyingDiener-West, Marie ;

Johns Hopkins University

关键词: HIV infection;    frailty;    regulatory T cells;    immune activation;    immunosenescence;    immune exhaustion;    MACS;    frailty phenotype;    Immunology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60322/ZHANG-DISSERTATION-2014.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

HIV infection and frailty, an aging-related syndrome, have been associated with chronic immune activation. This observation suggests a lack of control of the immune response in both conditions. T regulatory cells (Tregs) are CD4+ lymphocytes that suppress excessive immune responses. We hypothesized that low levels of Tregs might be responsible for the high levels of immune activation seen in frail people, whether they are HIV- or HIV+. To test this hypothesis, we studied HIV+ and HIV- men in the Multicenter AIDS Cohort Study (MACS), for whom the frailty phenotype (FP) has been assessed semiannually since 2007. We defined frailty as expression of the FP at 2 consecutive MACS study visits, and non-frailty as non-expression of the FP at 2 consecutive visits. Percentages and absolute counts of total Tregs (CD4+CD25+CD127low/- FoxP3+) and different subsets of Tregs were measured by flow cytometry, as were activated (HLA-DR+CD38+), senescent (CD28-, CD28-CD57-, or CD28-CD57+), and exhausted (PD-1+) T cells. In addition, the suppressive function of Tregs was measured in vitro.The results did not support our hypotheses. Specifically, percentages of Tregs were higher in frail men than in non-frail men, regardless of HIV status; percentages of subsets of Tregs and the suppressive function of Tregs did not differ by frailty status; and percentages of activated, senescent, and exhausted T cells in frail men were similar to or higher than those in non-frail men. A surprising finding was that while percentages of Tregs and activated T cells were negatively correlated in non-frail HIV- and HIV+ men and in frail HIV- men, this correlation was positive in frail HIV+ men. In addition, the correlation between Tregs and senescent CD4 T cells was also positive only in frail HIV+ men.These data suggest that: 1) despite having higher percentages of Tregs, Tregs in frail men, both HIV- and HIV+, do not inhibit chronic immune activation as those from non-frail men; and 2) the relationship of Tregs with activated T cells and senescent T cells differs by frailty status among HIV+ men. To conclude, the immunological correlates and/or mechanisms of frailty may differ by HIV status.