The CD4 molecule on CD8+ T lymphocytes directly enhances the immune response to viral and cellular antigens.

CD8+ T lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. We have previously demonstrated that costimulation of purified human CD8+ T cells induces de novo expression of the CD4 molecule and that ligation of CD4 on this cell type modulates CD8+ T cell activity in vitro. Herein, we investigate how the CD4 molecule expressed on murine CD8+ T cells contributes to CD8+ cell responses in vivo by employing adoptive transfer of CD8 cells from CD4 knockout mice into severe combined immunodeficient (SCID) recipients. Transfer of these cells into syngeneic SCID mice resulted in a decreased immune response to infection by lymphocytic choriomeningitis virus. These decreased responses occurred even in the presence of CD4+ T cells, indicating that this was truly a CD8-cell defect. Similarly, transfer of CD8+ T cells incapable of expressing CD4 into allogeneic SCID mice resulted in a decreased response to alloantigens compared with that of normal CD8+ T cells. Therefore, CD4 expression on CD8 T lymphocytes modulates cytotoxic T lymphocyte function and is critical in vivo for optimal cell-mediated immunity to viral and alloantigens.