Immediate-early host-virus interactions that occur during the first weeks after HIV infection have a major impact on disease progression. The mechanisms underlying the failure of HIV-specific CD8 T-cell response to persist and control viral replication early in infection are yet to be characterized. In this study, we performed a thorough phenotypic, gene expression and functional analysis to compare HIV-specific CD8 T cells in acutely and chronically infected subjects.We showed that HIV-specific CD8 T cells in primary infection can be distinguished by their metabolic state, rate of proliferation, and susceptibility to apoptosis. HIV-specific CD8 T cells in acute/early HIV infection secreted less IFN-␥ but were more cytotoxic than their counterparts in chronic infection. Importantly, we showed that the levels of IL-7R expression and the capacity of HIV-specific CD8 T cells to secrete IL-2 on antigenic restimulation during primary infection were inversely correlated with the viral set-point. Altogether, these data suggest an altered metabolic state of HIV-specific CD8 T cells in primary infection resulting from hyperproliferation and stress induced signals, demonstrate the discordant function of HIV-specific CD8 T cells during early/acute infection, and highlight the importance of T-cell maintenance for viral control. (Blood. 2012;120(17):3466-3477)

Persistence of memory CD81 T cells is known to be largely controlled by common gamma chain cytokines, such as IL-2, IL-7 and IL-15. However, other molecules may be involved in this phenomenon. We show here that TLR2 À/À mice have a decreased frequency of memory phenotype CD8 1 T cells when compared with WT mice. This prompted us to investigate the role of TLR2 in the homeostasis of memory CD8 1 T cells. We describe here a new TLR2-dependent mechanism which, in the absence of specific antigen, directly controls memory CD8 1 T-cell proliferation and IFN-c secretion. We demonstrate that TLR2 engagement on memory CD8 1 T cells increases their proliferation and expansion induced by IL-7 both in vitro and in vivo. We also show that TLR2 ligands act in synergy with IL-2 to induce IFN-c secretion in vitro. Both conclusions are obtained with spontaneously arising memory phenotype and antigen-specific memory CD8 1 T cells. Altogether, our data support the idea that continuous TLR2 signaling in response to microbial stimuli or endogenous danger signals might directly contribute to the maintenance of the diversity memory CD8 1 T cells in the organism.

PURPOSE.The purpose of the present study was to evaluate the cellular response to microbial antigens in patients with idiopathic uveitis. METHODS. Blood lymphocytes from 31 patients with uveitis and 24 healthy controls were cultivated with microbial antigens and analyzed by flow cytometry after staining with monoclonal antibodies against CD3, CD4, and activation markers CD69 and CD25. RESULTS. Although no difference was noted in circulating lymphocytes, the activation of T cells, detected with CD69, was higher in 24-hour blood culture from uveitis patients with Candida albicans antigen (Ca-Ag) than from controls, especially in posterior uveitis and panuveitis. Moreover, late response, detected with CD25, to different microbial antigens was higher in patient with uveitis. CONCLUSIONS. Such results suggest the role of Ca-Ag and microbial antigens in the pathogenic mechanisms of idiopathic uveitis. (Invest Ophthalmol Vis Sci.