Tolerogenic ability of thymocytes in organ-cultured thymus lobes.

It is generally believed that macrophages and dendritic cells are the major cell populations that present tolerogenic self antigens to developing thymocytes. However, it is still controversial whether self antigens expressed on thymocytes themselves work as tolerogens in the thymus. To evaluate this possibility, Thy-1 bright cells were sorted out from fetal thymus cells on the 15th gestation day, and were colonized into 2'-deoxyguanosine-treated allogeneic thymus lobes. The repopulated thymus lobes were organ-cultured, and the allo-specific killer activity of thymocytes recovered from the lobes was examined. These cells were tolerant to class I but not to class II-MHC of the donor haplotype, indicating that class I molecules expressed on the thymocytes worked as tolerogen. Tolerogenic ability of Thy-1+ cells was also demonstrated in another system. Upon intimate contact with allogeneic thymus lobes on a polycarbonate filter, thymus lobes fused with each other and Thy-1+ cells co-migrated (Eur. J. Immunol. 19:1525-1530, 1989). In thymus lobes rendered parabiotic from day 5, CTL tolerance was achieved against class I but not to class II MHC. These data indicate that thymocyte-thymocyte interaction is sufficient to induce class I CTL tolerance in developing thymocytes.