Appearance of Extrathymic Early Differentiated CD4-CD8- T Cells with T Cell Receptor γ/δ or α/β after Thymus Grafting to Nude Mice: Influence of Thymus on Extrathymic T Cell Differentiation

Fetal thymus grafting into athymic nude mice has been used as an experimental model of T cell development. To understand the early events of T cell development, we have examined the sequence of appearance of T cell subsets in lymph nodes (LN) of BALB/c nu/nu mice after grafting with syngeneic fetal thymus. T cells expressing T cell receptor (TCR) α/β or γ/δ increased in LN from 1 week after grafting, although no host-derived CD3+ T cells were detected in the grafted thymus and no donor thymus-derived T cells were detected in the LN. The early appearing T cells of both TCR α/β and TCR γ/δ showed a CD4-CD8- phenotype. V region usage analysis of the early appearing TCR γ/β T cells revealed that they contained cells bearing Vβ3 or Vβ11, which are potentially reactive to self-superantigen MIs-2a or Dvb11, respectively, and are deleted in the course of T cell development in the thymus of euthymic BALB/c mice. The early appearing T cells showed neither mixed lymphocyte reaction nor cytotoxic T cell activity against allogeneic cells. In contrast, lymphokine-activated killer cells from early appearing T cells, which contained high percentages of TCR γ/δ T cells, exhibited higher cytotoxic activity against P815 mastocytoma than those from euthymic mice or untreated nude mice. All these results suggest that the early appearing T cells are developed extrathymically. We propose that the thymus may induce extrathymic T cell development without direct cell-to-cell interaction. It seems likely that the extrathymically developed T cells, especially TCR γ/δ T cells, induced by the thymus have some role in the defense mechanism in the absence of conventional thymus-derived T cells.