RAG1, RAG2 and pre-T cell receptor alpha chain expression by adult human hepatic T cells: Evidence for extrathymic T cell maturation

Flow cytometric analysis of cell suspensions obtained from normal adult liver tissue at the time of transplantation revealed significant populations of T lymphocytes. These were examined for molecular evidence of local T cell maturation using reverse transcription-polymerase chain reaction to detect expression of recombination activation gene 1 (RAG1), RAG2 and pre-T cell receptor alpha chain (pT alpha), which occurs only in early thymocyte development. Four specimens of whole liver were positive for RAG1 and RAG2 expression, whereas peripheral blood mononuclear cells from the same individuals were negative. To localize RAG expression, immature (CD2(+)CD7(+)) and mature (CD45R0(+))T cell subpopulations were isolated by magnetic separation from hepatic and peripheral blood mononuclear cell preparations. We detected the expression of RAGI, RAG2 and pre-TCR alpha in five specimens of hepatic CD2(+)CD7(+) but not in CD45RO(+) hepatic lymphocytes. Four out of six specimens of CD2(+)CD7(+) cells from the peripheral blood were negative for RAG1 and RAG2 while all six specimens were positive for pT alpha expression. These results suggest that pre-T cells are trafficking from the bone marrow or the thymus to other tissues to continue differentiation and selection in the context of an appropriate cellular and molecular environment. The presence of immature populations of T cells in the adult liver and high levels of RAG expression suggests that the adult liver provides such an environment for extrathymic T cell maturation. These findings may have important implications for tolerance induction after liver transplantation and offer help in understanding the etiology of autoimmune liver disease.