In the same regard, whereas specific responses are necessary for IRIS, unspecific mechanisms http://www.selleckchem.com/products/3-deazaneplanocin-a-dznep.html such as innate mediators [5,33] may also be recruited depending on the manifestation. Consistent with the concept of characteristic mediators of particular IRIS forms, increased percentages of blood CD8+ T cells specifically predict mycobacterial IRIS [16]. In the present study, we report that in patients that develop tuberculous IRIS, CD8+ T cells have a markedly increased naive subpopulation, in which an expansion of activated cells coincides with the manifestation of TB IRIS. An expansion of naive CD8+ T cells and a later decrease in EM CD8+ T cells were unique to TB IRIS patients during part of the follow-up period. A possible explanation to this observation could be migration of EM CD8+ T cells to inflamed tissues.

Although cellular responses to M. tuberculosis antigens are commonly detected through class II MHC presentation to CD4+ T cells [34], CD8+ T cells also take part in the specific response to M. tuberculosis infection [35-39], even in the absence of CD4+ T cell activity [40]. In this regard, CD8+ T cell recruitment to the lung has been demonstrated in animal tuberculosis models [41], and by the presence of CD8+ T cells in pleural effusions from patients with active tuberculosis [42]. Verification of this possibility will require the detection of Mycobacterium tuberculosis- specific cells at the inflamed tissues of persons with TB IRIS. In any case, the expansion of naive CD8+ T cells in TB IRIS patients could reflect a homeostatic response to EM CD8+ T cell recruitment and turnover [43] and not necessarily specific responses against M.

tuberculosis. HAART normally decreases the frequency of CD38+ HLADR+ (activated) T cells [44,45]. However, we found an expansion of CD38+ HLADR+ CD8+ T cells, particularly naive CD8+ T cells, peaking during the presentation of TB IRIS episodes. The frequency of activated CD38+ HLADR+ CD8+ T cells is a strong independent predictor of HIV disease progression [46,47] and is related to inflammation in chronic HIV infection [48]. Although no mechanistic link is demonstrated here, our findings pose the question of whether activation is a driver or a consequence of IRIS and whether the control of activation might prevent IRIS [8]. Of importance, even though TB IRIS patients started HAART with a higher absolute count of total naive CD8+ T cells (Figure 1A), only the counts of their HLADR+ CD38+ fraction expanded after HAART (Figure 4E). The absolute counts of this activated fraction of naive CD8+ T cells did not differ before treatment (week 0). Therefore, the observed increase is not reflecting basal differences, but rather, a real expansion Cilengitide of HLADR+ CD38+ naive CD8+ T cells.