Forced expression of terminal deoxynucleotidyl transferase in fetal thymus resulted in a decrease in γδ T cells and random dissemination of Vγ3Vδ1 T cells in skin of newborn but not adult mice

The repertoire of lymphocyte receptor genes encoded in a germline is further diversified by a number of processes, including the template-independent addition of nucleotides (N regions) by means of terminal deoxynucleotidyl transferase (TdT). Normally, mouse gamma delta T cells in the early fetal thymus, whose T-cell receptor (TCR) genes lack N regions and are encoded by V gamma 3-J gamma 1 and V delta 1-D delta 2-J delta 2 with canonical junctions (invariant V gamma 3V delta 1), are thought to be the precursors of dendritic epidermal T cells (DETC). We generated mutant mice whose endogenous TdT promoter was replaced with the lck promoter through homologous recombination. These mutant mice expressed TdT in fetal thymus, had abundant N regions and infrequent canonical junctions in gamma and delta rearrangements, and showed a decreased number of gamma delta T cells. Various V gamma 3V delta 1 T cells, most of which had N regions in their TCR genes, were found to disseminate in the skin of newborn mutant mice, whereas normal numbers of DETCs with the invariant V gamma 3V delta 1 rearrangement were observed in adult mutants. These data demonstrate that the regulation of TdT expression during fetal development is important for the generation of gamma delta T cells, and that V gamma 3V delta 1 T cells, which have various junctional sequences in their TCR genes, randomly disseminate in skin, but invariant V gamma 3V delta 1 T cells have a great advantage for proliferation in skin.