Predominant appearance of gamma/delta T lymphocytes in the liver of mice after birth

gamma/delta 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 gamma/delta T cell receptor (TcR). Previous human and murine studies have shown that a high proportion of gamma/delta T cells reside in the liver and that such liver gamma/delta T cells have lymphoblastic morphology and can spontaneously proliferate in vitro. In the present study, a predominant appearance of gamma/delta T cells (up to 23% among CD3+ cells) in the liver was confirmed in 4-week old mice of various strains. gamma/delta T cells in the liver preferentially co-expressed CD8 antigens, whereas the vast majority of gamma/delta T cells in the spleen lacked the CD8 antigens. The identification of gamma/delta T cells in various lymphoid and non-lymphoid organs also revealed the liver to be one of the organs where gamma/delta T cell are most abundant. The level of such liver gamma/delta T cells showed a clear age-related variation. In the fetal stage and just after birth, gamma/delta T cells were not detectable in the liver (less than 0.2%). However, a significantly higher percentage of gamma/delta 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 gamma/delta T cells also increased as a function of age. V gene segment usage analysis by the polymerase chain reaction method demonstrated that V gamma 1 or V gamma 2/V delta 6 were preferentially used by liver gamma/delta T cells. The age-related increase of gamma/delta T cells was more prominent in the liver of athymic nude mice, and such gamma/delta T cells highly co-expressed the CD8 antigens and also utilized the V gamma 1 or V gamma 2/V delta 6 for gamma/delta Tcr. The predominant appearance of unique gamma/delta T cells in the liver, which was inversely related to the existence of the thymus, indicates that these gamma/delta T cells may differentiate extrathymically in the liver.