Regulatory T cells, frailty, and immune activation in men who have sex with men in the multicenter AIDS cohort study

Background. Both HIV infection and frailty have been associated with chronic immune activation. One possible explanation for this chronic immune activation could be low levels of CD4⁺ T regulatory cells (T_regs), which suppress immune responses. Methods. HIV-uninfected (HIV-) and HIV-infected (HIV+) men in the Multicenter AIDS Cohort Study (MACS) were classified as frail (or nonfrail) if they expressed (or did not express) the Fried frailty phenotype at two consecutive study visits. Percentages and absolute numbers of total T_regs, and percentages of different subsets of T_regs and of activated T cells were measured by flow cytometry. The function of T_regs was measured by suppression of T-cell proliferation. Results. Percentages of T_regs were higher, rather than lower, in frail men than in nonfrail men, and this difference was significant for HIV-men. Percentages of subsets of T_regs did not differ significantly by frailty status. Among HIV+ men, the suppressive function of T_regs was similar between frail and nonfrail men. Percentages of T_regs and activated T cells were negatively correlated in nonfrail men (HIV-and HIV+) and in frail HIV-men, but this correlation was strongly positive in frail HIV+ men. Conclusion. These data suggest that: (a) T_regs were not deficient in frail men; and (b) the immunological pathophysiology of frailty may differ by HIV status.