CD8+ T-cells suppress antigen-specific and allogeneic CD4+ T-cell responses to herpes simplex virus type 2-infected human dendritic cells

In this study we show that human dendritic cells (DC), productively infected with herpes simplex virus type 2 (HSV-2), activate CD8+ T cells that suppress antigen-specific and alloreactive CD4+ T cell expansion. Addition of CD8+ T cells to cultures of DC and CD4+ T cells blocked CD4+ T-cell proliferation in response to HSV-2-infected but not to uninfected DC. The effect was independent of prior HSV exposure or cognate MHC class I-restricted CD8-DC recognition as it was induced in CD8+ T cells from HSV-2-seronegative individuals and in mixed lymphocyte reactions using allogeneic DC. Both CD8+ CD25+ and CD8+ CD25- cells were shown to have suppressive capacities. The blood-derived CD25+ CD8+ T cells did not express Foxp3 mRNA but had a bona fide antiproliferative capacity in response to both uninfected and HSV-2-infected DC, whereas the CD25-CD8+ T cells were selectively activated to become antiproliferative by HSV-2-infected DC. These data imply that HSV infection of DC could modulate the immune response by activating CD8+ T cells.