Trophoblastic cells lack classical HLA class I and class II molecules but express HLA-G1. Although this may prevent allorecognition by maternal T cells, it renders trophoblastic cells potentially susceptible to lysis by natural killer (NK) cells. As shown here, only a fraction of peripheralblood NK cells in pregnant women express the HLA-G1-specific CD94͞NKG2A and͞or LIR-1 receptors. However, all NK cells isolated from maternal decidua during the first trimester expressed either one or both of these receptors. Perhaps more importantly, a fraction of cells expressed p49, an HLA-G1-specific inhibitory receptor, undetectable in peripheral-blood NK cells. p49 was expressed on virtually all NK cells isolated from placenta at term. Functional analyses revealed that the HLA class I-negative 221 lymphoblastoid cell line transfected with HLA-G1 was only partially protected from lysis by peripheral-blood NK cells isolated from pregnant women, whereas it was fully protected from decidual NK cells. As indicated by the addition of specific antibodies to cytolytic tests, all the above receptors contributed to HLA-G1 recognition by decidual NK cells, although p49 would appear to play a predominant role.

and CD8؉ cells expressed CD94, the simultaneous expression of NKG2A (i.e., the other component of the CD94͞NKG2A inhibitory NKR) was confined to CD8 ؉ cells. Similar data were obtained in T cell populations activated in mixed lymphocyte cultures in the presence of IL-15. The expression of CD94͞NKG2A led to an impairment of allo-specific cytolytic activity by mixed lymphocyte culture-derived T cell populations or clones. Remarkably, cytolysis could be restored by the addition of anti-CD94 mAb, i.e., by masking the inhibitory NKRs.

Different HLA class I-specific killer inhibitory receptors (KIR) are expressed in vivo by a fraction of activated T cells, predominantly CD8+ , in which 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-g (TGF-g ) in T cells responding to bacterial superantigens in vitro. We show that TGF-g 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-g concentrations which have no substantial effect on lymphocyte proliferation. Maximal CD94 expression occurred when TGF-g was added shortly after the cells were placed in culture. No expression could be induced 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 redirected killing assay using the Fc + receptor-positive P815 murine target cells.