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 expansions of these cells have been reported in both healthy and diseased individuals, the functional properties of the CD4⁺CD8^dim population are largely unknown. In this study, we examined antigen-specific cytokine and proliferative responses of the CD4⁺CD8^dim subset. In whole blood cultures stimulated with the viral antigens HCMV and HIV-1, a significant fraction of the CD4⁺CD8^dim subset exhibited cytokine expression and proliferation in response to antigen activation. Typically, the CD4⁺CD8^dim population contained two- to eightfold higher frequencies of antigen-specific cytokine producing cells than the CD4⁺CD8^- population. Phenotypic analysis of the cytokine expressing CD4⁺CD8^dim population indicated that these cells are memory T cells, with a high frequency of this population expressing the cytotoxic markers CD56 and perforin. Furthermore, the CD4⁺CD8^dim cytokine responses to CMV were shown to be MHC class II dependent. Significantly, purified CD4⁺CD8^dim T cells were found to possess higher CMV-specific cytotoxic activity than purified CD4⁺CD8^- T cells in a standard ⁵¹Cr-release CTL assay. Thus, CD4⁺CD8^dim T cells appear to be MHC class II dependent, are capable of cytolytic effector activity, and are highly enriched within the CD4⁺ cell populations specific for HCMV and HIV-1.