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Abstract
BackgroundCD4+ 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.MethodsWe 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.ResultsTB 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.ConclusionsCD8+ 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.
Highlights
CD4+ T cell activation indicators have been reported to be a common phenomenon underlying diverse manifestations of immune reconstitution inflammatory syndrome (IRIS)
We have previously found that increased frequencies of blood CD8+ T cells predict the occurrence of Immune reconstitution inflammatory syndrome (IRIS) related to mycobacterial infections (Mycobacterium tuberculosis and Mycobacterium avium complex (MAC)) [16], suggesting that alterations in CD+8 T cells are characteristic of mycobacterial IRIS
We report an expansion of activated CD8 T cells, of the naive subpopulation, concomitant with TB IRIS, unlike other IRIS forms
Summary
CD4+ T cell activation indicators have been reported to be a common phenomenon underlying diverse manifestations of immune reconstitution inflammatory syndrome (IRIS). The potential severity of IRIS has spawned research on its prediction [4,5,6], cell populations that are characteristic of particular IRIS manifestations; each IRIS form has unique inflammatory manifestations that are characteristic of the opportunistic infection that is paradoxically worsened or unmasked by immune reconstitution [14,15]. We have previously found that increased frequencies of blood CD8+ T cells predict the occurrence of IRIS related to mycobacterial infections (Mycobacterium tuberculosis and Mycobacterium avium complex (MAC)) [16], suggesting that alterations in CD+8 T cells are characteristic of mycobacterial IRIS. We report an expansion of activated CD8 T cells, of the naive subpopulation, concomitant with TB IRIS, unlike other IRIS forms
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