Transforming growth factor-beta-induced expression of CD94/NKG2A inhibitory receptors in human T lymphocytes

Different HLA class I-specific killer inhibitory receptors (KIR) are expres sed in vivo by a fraction of activated T cells, predominantly CD8(+), in wh ich they may inhibit TCR-mediated cell functions. In an attempt to identify mechanisms leading to KIR expression in T cells, we analyzed the effect of transforming growth factor-beta (TGF-beta) in T cells responding to bacter ial superantigens in vitro. We show that TGF-beta induces the expression of CD94/NKG2A in cells responding to toxic shock syndrome toxin 1 or to other staphylococcal superantigens. Remarkably, maximal CD94 expression occurred at (low) TGF-beta concentrations which have no substantial effect on lymph ocyte proliferation. Maximal CD94 expression occurred when TGF-beta was add ed shortly after the cells were placed in culture. No expression could be i nduced in CD94/NKG2A-negative T cell clones. Although both CD4(+) and CD8() expressed CD94, the simultaneous expression of NKG2A was mostly confined to CD8+ cells. Monoclonal antibody-mediated cross-linking of CD94/NKG2A led to an impairment of T cell triggering via CD3, as determined in a redirect ed killing assay using the Fc gamma receptor-positive P815 murine target ce lls.