The role of TCR stimulation and TGF-β in controlling the expression of CD94/NKG2A receptors on CD8 T cells

Following antigen recognition, murine CD8 T cells express CD94/NKG2A receptors. Our results show that this up-regulation occurs rapidly in vitro and is accompanied by an ∼8-fold increase in CD94 and ∼125-fold increase in NKG2A mRNA. In contrast, only a twofold increase in NKG2C mRNA is noted. The addition of TGF-β, but not IL-10, IL-12 or IL-15, leads to a further increase in cell membrane expression of these receptors, as well as a ∼6-fold increase in mRNA for both chains. TGF-β also increases CD94/NKG2A expression on memory CD8 T cells that are re-exposed to antigen. The effect of TGF-β on increasing CD94/NKG2A expression on both naive and memory CD8 T cells occurs only when there is a concurrent stimulation through the TCR. In contrast, TGF-β does not increase expression of CD94/NKG2A on resting or activated NK cells. We also show by using purified CD8 T cells, that TGF-β acts directly on these cells. These results implicate a role for both antigen and TGF-β in increasing expression of inhibitory CD94/NKG2A receptors on CD8 T cells.