CD4(+)CD8(dim) T lymphocytes exhibit enhanced cytokine expression, proliferation and cytotoxic activity in response to HCMV and HIV-1 antigens

CD4(+)CD8(dim) T cells represent a minor subset of the total CD3(+) T cell population in peripheral blood. Although transient and persistent expansion s of these cells have been reported in both healthy and diseased individual s, the functional properties of the CD4(+)CD8(dim) population are largely u nknown. In this study, we examined antigen-specific cytokine and proliferat ive responses of the CD4(+)CD8(dim) subset. In whole blood cultures stimula ted with the viral antigens HCMV and HIV-1, a significant fraction of the C D4(+)CD8(dim) subset exhibited cytokine expression and proliferation in res ponse to antigen activation. Typically, the CD4(+)CD8(dim) population conta ined two- to eightfold higher frequencies of antigen-specific cytokine prod ucing cells than the CD4(+)CD8(-) population. Phenotypic analysis of the cy tokine expressing CD4(+)CD8(dim) population indicated that these cells are memory T cells, with a high frequency of this population expressing the cyt otoxic markers CD56 and perforin. Furthermore, the CD4(+)CD8(dim) cytokine responses to CMV were shown to be MHC class II dependent. Significantly, pu rified CD4(+)CD8(dim) T cells were found to possess higher CMV-specific cyt otoxic activity than purified CD4(+)CD8(-) T cells in a standard Cr-51-rele ase CTL assay. Thus, CD4(+)CD8(dim) T cells appear to be MHC class II depen dent, are capable of cytolytic effector activity, and are highly enriched w ithin the CD4(+) cell populations specific for HCMV and HIV-1.