Appearance of extrathymic early differentiated CD4-CD8- T cells with T cell receptor gamma/delta or alpha/beta 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) alpha/beta or gamma/delta 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 alpha/beta and TCR gamma/delta showed a CD4-CD8- phenotype. V region usage analysis of the early appearing TCR alpha/beta T cells revealed that they contained cells bearing V beta 3 or V beta 11, which are potentially reactive to self-superantigen Mls-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 gamma/delta 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 gamma/delta T cells, induced by the thymus have some role in the defense mechanism in the absence of conventional thymus-derived T cells.