Predominant appearance of γ/δ T lymphocytes in the liver of mice after birth

Abstract

γ/δ T lymphocytes residing in the liver of mice were systematically characterized with respect to their age‐related variation, phenotype and V gene segment usage of γ/δ T cell receptor (TcR). Previous human and murine studies have shown that a high proportion of γ/δ T cells reside in the liver and that such liver γ/δ T cells have lymphoblastic morphology and can spontaneously proliferate in vitro. In the present study, a predominant appearance of γ/δ T cells (up to 23% among CD3⁺ cells) in the liver was confirmed in 4‐week old mice of various strains. γ/δ T cells in the liver preferentially co‐expressed CD8 antigens, whereas the vast majority of γ/δ T cells in the spleen lacked the CD8 antigens. The identification of γ/δ T cells in various lymphoid and non‐lymphoid organs also revealed the liver to be one of the organs where γ/δ T cell are most abundant. The level of such liver γ/δ T cells showed a clear age‐related variation. In the fetal stage and just after birth, γ/δ T cells were not detectable in the liver (< 0.2%). However, a significantly higher percentage of γ/δ T cells among both the total population of mononuclear cells and CD3⁺ cells was detected in the liver of young 2‐ to 8‐week‐old mice; this percentage subsequently declined. As the total number of liver mononuclear cells increased in aged mice, the absolute number of liver γ/δ T cells also increased as a function of age. V gene segment usage analysis by the polymerase chain reaction method demonstrated that V_γ1 or V_γ2/V_δ6 were preferentially used by liver γ/δ T cells. The age‐related increase of γ/δ T cells was more prominent in the liver of athymic nude mice, and such γ/δ T cells highly co‐expressed the CD8 antigens and also utilized the V_γ1 or V_γ2/V_δ6 for γ/δ TcR. The predominant appearance of unique γ/δ T cells in the liver, which was inversely related to the existence of the thymus, indicates that these γ/δ T cells may differentiate extrathymically in the liver.