SummaryThe participation of CD94 and NKG2 gene family members in the function of NK cells and CD8 + cytolytic cells has recently been addressed in detail. However, the role that these molecules play in the key CD4 + regulatory cells remains largely unexplored. This study has examined the expression and regulation of CD94 and NKG2 genes in purified human peripheral CD4 + cells stimulated with several agents. We found a constitutive expression of NKG2-E in CD94-depleted resting peripheral CD4 + cells, whereas inductions of NKG2-A and NKG2-C required chronic cell activation and occurred after expression of CD94. We found that CD3-mediated stimulation induces the expression of CD94 first by day 5 of culture, followed by NKG2-A by day 15 and finally NKG2-C, which is not detected until 20 days after repeated stimulation. This pattern of gene expression differs sharply from that observed in purified CD8 + T cells, where mRNA from all NKG2 gene family members are detected after 5 days of stimulation. Selective activation of TCR V β 2 -bearing cells with toxic shock syndrome toxin-1 superantigen reveals that mRNA induction of NKG2-A and NKG2-C genes is significantly influenced by the presence of cytokines (IL-10 and TGF-β ) and by the restimulation of the cells. In addition, the occupancy of the CD94/NKG2-A receptor expressed on these superantigen-stimulated CD4 + T lymphocytes abrogates TNF-α and IFN-γ production, whereas NKG2-C enhances production of these cytokines. Taken together our results reveal strict gene regulatory mechanisms for CD94 and NKG2 gene expression on CD4 + cells that are different from those governing the expression of these same genes in CD8 + cells. The results suggest that these genes also participate in chronic CD4 + T-cell responses.

No abstract