On the mechanisms of thymic epithelium induced tolerance

We have devised a model in which nude mice are T cell reconstituted at birth by subcutaneous grafts of embryonic thymic epithelium (TE) removed from 10 days allogeneic embryos. The TE is colonized by the nude mouse hemopoietic cells which differentiate into T cells. Such T cell-reconstituted nude mice are able to reject third party skin graft and are tolerant to skin of their own haplotype but also the TE H-2 type. We have recently shown that this tolerance can be transferred by CD4+ peripheral T cells selected on the allogeneic TE. The question as to whether such T cells can regulate the activity of effector cells from normal mice is addressed here. We show that the transfer of peripheral T cells issued from such chimeras, together with syngeneic T cells from normal mice, into nude recipients induces a significant delay in the rejection of skin graft of the TE haplotype. This delay depends on the ratio of the 2 types of injected cells. This demonstrates that regulatory T cells selected on an allogeneic TE are able to control the effector activity of peripheral T cells issued from normal mice. The T cells selected on the allogeneic TE can therefore be considered as endowed with a negative regulatory activity with respect to the process leading to effector cells activation.