Transient expansion of activated CD8+ T cells characterizes tuberculosis-associated immune reconstitution inflammatory syndrome in patients with HIV: a case control study

Background: CD4(+) T cell activation indicators have been reported to be a common phenomenon underlying diverse manifestations of immune reconstitution inflammatory syndrome (IRIS). However, we have found that a high frequency of circulating CD8(+) T cells is a specific risk factor for mycobacterial IRIS. Therefore, we investigated whether CD8(+) T cells from patients who develop TB IRIS were specifically activated. Methods: We obtained PBMCs from HIV+ patients prior to and 4, 8, 12, 24, 52 and 104 weeks after initiating antiretroviral therapy. CD38 and HLADR expression on naive, central memory and effector memory CD8(+) and CD4(+) T cells were determined by flow cytometry. Absolute counts and frequencies of CD8(+) T cell subsets were compared between patients who developed TB IRIS, who developed other IRIS forms and who remained IRIS-free. Results: TB IRIS patients showed significantly higher counts of naive CD8(+) T cells than the other groups at most time points, with a contraction of the effector memory subpopulation occurring later in the follow-up period. Activated (CD38(+) HLADR(+)) CD8(+) T cells from all groups decreased with treatment but transiently peaked in TB IRIS patients. This increase was due to an increase in activated naive CD8(+) T cell counts during IRIS. Additionally, the CD8(+) T cell subpopulations of TB IRIS patients expressed HLADR without CD38 more frequently and expressed CD38 without HLADR less frequently than cells from other groups. Conclusions: CD8(+) T cell activation is specifically relevant to TB IRIS. Different IRIS forms may involve different alterations in T cell subsets, suggesting different underlying inflammatory processes.