Non-MHC-restricted CD4(+) T lymphocytes are regulated by HLA-Cw7-mediated inhibition

Natural killer cells (NK cells) represent an important component of innate immunity with the capacity to kill many turner and virus-infected cells. Th e discovery of several classes of killer cell inhibitory receptors expresse d by NK cells chat bind specific MHC class I ligands on target cells provid es detailed insight into the regulation of NK cells. Inhibitory receptors d eliver negative signals following MHC ligand binding that abrogate cytotoxi city and, thus, determine the specificity of NK effector cell function. Her e, we describe a novel subset of human memory CD4(+) T lymphocytes that dis play an NK-like pattern of regulation. These CD4(+) T cells display non-MHC -restricted cytotoxicity chat is governed by HLA-Cw7 mediated inhibition. I n NK cells, such specificity is associated with expression of the inhibitor y receptor p58.2. In contrast, neither p58.2 nor other known inhibitory rec eptors were detected on these non-MHC-restricted CD4(+) T cells. This sugge sts that these cells are regulated by a hitherto unknown inhibitory recepto r. The finding that interactions with MHC molecules downregulate the functi on of these CD4(+) T cells suggests that these non-MHC-restricted T cells m ay function to detect and eliminate cells with aberrant MHC expression. (C) American Society for Histocompatibility and Immunogenetics, 2000. Publishe d by Elsevier Science Inc.