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) remo ved from 10 days allogeneic embryos. The TE is colonized by the nude m ouse hemopoietic cells which differentiate into T cells. Such T cell-r econstituted nude mice are able to reject third party skin graft and a re tolerant to skin of their own haplotype but also the TE H-2 type. W e 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 fr om normal mice, into nude recipients indices a significant delay in th e rejection of skin graft of the TE haplotype. This delay depends on t he ratio of the 2 types of injected cells. This demonstrates that regu latory T cells selected on an allogeneic TE are able to control the ef fector activity of peripheral T cells issued from normal mire. The T c ells selected on the allogeneic TE can therefore be considered as endo wed with a negative regulatory activity with respect to the process le nding to effector cells activation.