| The Tim-3+ T cells in HIV infection are dysfunctional in proliferation or cytokine production. Here, we evaluated the effects of Tim-3 expression on the cytotoxicity of CD8+ T cells in HIV infection by examining 1) the ability of Tim-3+ CD8 + T cells to make perforin and 2) the direct ability of Tim-3 + CD8+ T cells to kill HIV infected CD4+ target cells. Tim-3+ CD8+ T cells maintained higher levels of perforin. However, these cells were defective in their ability to degranulate. Blocking the Tim-3 signalling pathway enhanced the cytotoxic capabilities of HIV specific CD8+ T cells by increasing: their degranulation capacity, their ability to release perforin, their ability to target activated granzyme B to HIV antigen expressing CD4+ T cells and their ability to suppress HIV infection of CD4+ T cells. Thus, the Tim-3 receptor can down-regulate the CD8+ T cell cytotoxicity through inhibition of degranulation and perforin/granzyme secretion. |
