Natural T cells in the human liver: Cytotoxic lymphocytes with dual T celland natural killer cell phenotype and function are phenotypically heterogenous and include V alpha 24-J alpha Q and gamma delta T cell receptor bearing cells

The adult liver contains lymphocytes with a unique phenotypic distribution compared to blood and other organs. We have characterized a human lymphocyt e population that exhibits dual T cell and natural killer (NK) cell phenoty pe and function, denoted natural T (NT) cells, in nine normal adult liver s pecimens. Flow cytometry revealed char up to 55% (mean 27%) of hepatic (but <6% of peripheral) CD3(+) lymphocytes expressed CD56, CD161 and/or one or more of the killer inhibitory receptors (KIR) p58.1, p58.2, p70 and CD94. N K function was attributed to the CD3(+)CD56(+) cells by the demonstration c hat hepatic, but not peripheral, CD3(+) lymphocytes could be induced to lys e NK-sensitive K562 target cells, while CD56(-) cells from both compartment s could not. Three color flow cytometric analysis of fresh hepatic cells in dicated that CD3(+)CD56(+) NT cells can be either CD8(+), CD4(+) or CD4(-)C D8(-), they express alpha beta or gamma delta T cell receptors (TCR) and CD 161 and KIRs, but rarely CD16. Hepatic NT cells predominantly express the m ature/activated CD45RO and CD56(dim) phenotypes. Analysis of mRNA productio n by isolated NT cells indicated a preferential usage of the invariant CD1- restricted V alpha 24-J alpha Q TCR. The presence of such large numbers of chronically activated NT cells provides compelling evidence that the liver has unique immunoregulatory functions. (C) American Society for Histocompat ibility and Immunogenetics, 1999 Published by Elsevier Science Inc.