Mounting evidence suggests that the upregulation of several inhibitory regulatory receptors on the surface of CD8(+) T cells during HIV-1 infection may contribute directly to the impairment of T-cell function. Here, we investigated the role of killer immunoglobulin receptors (KIR), which are expressed on NK cells and on CD8(+) T cells, in regulating CD8(+) T-cell function in HIV-1 infection. KIR expression was progressively upregulated on CD8(+) T cells during HIV-1 infection and correlated with the level of viral replication. Expression of KIR was associated with a profound inhibition of cytokine secretion, degranulation, proliferation, and activation by CD8(+) T cells following
stimulation with T-cell receptor (TCR)-dependent stimuli. selleck compound In contrast, KIR+ CD8(+) T cells responded potently to TCR-independent stimulation, demonstrating that these cells are functionally competent. KIR-associated suppression of CD8(+) T-cell function was independent of ligand engagement, suggesting that these regulatory receptors may constitutively
repress TCR activation. This ligand-independent repression of TCR activation of KIR+ CD8(+) T cells may represent a significant barrier to therapeutic interventions aimed at improving the quality of the HIV-specific Saracatinib cell line CD8(+) T-cell response in infected individuals.”
“In primary infection, CD8(+) T cells are important for clearance Bafilomycin A1 supplier of infectious herpes simplex virus (HSV) from sensory ganglia. In this study, evidence of CD8(+) T-cell-mediated clearance of infectious HSV type 1 (HSV-1) from neural tissues
was also detected. In immunocompetent mice, HSV-specific CD8(+) T cells were present in sensory ganglia and spinal cords coincident with HSV-1 clearance from these sites and remained detectable at least 8 months postinfection. Neural CD8(+) T cells isolated at the peak of neural infection secreted gamma interferon, tumor necrosis factor alpha, interleukin-2 (IL-2), or IL-4 after stimulation with HSV antigen. HSV-1 titers in neural tissues were greatly reduced over time in CD8(+) T-cell-deficient and CD8(+) T-cell-depleted mice, suggesting that CD8(+) T cells could mediate clearance of HSV-1 from neural tissue. To examine possible mechanisms by which CD8(+) T cells resolved neural infection, CD8(+) T cells were depleted from perforin-deficient or FasL-defective mice. Clearance of infectious virus from neural tissues was not significantly different in perforin-deficient or FasL-defective mice compared to wild-type mice. Further, in spinal cords and brains after vaginal HSV-1 challenge of chimeric mice expressing both perforin and Fas or neither perforin nor Fas, virus titers were significantly lower than in control mice. Thus, perforin and Fas were not required for clearance of infectious virus from neural tissues.