Transplantation tolerance: evidence for Lyt 1+,2-,Qa 1.2+ Suppressor-inducer T cells in allogeneic thymus-grafted nude mice.

Nude mice, of BALB/c genotype, grafted with thymus stroma become immunocompetent (R. Hong, H. Schultz-Wisserman, E. Jarreth-Toth, S. D. Horowitz, and D.D. Manning, J. Exp. Med. 149, 398, 1979; B. P. Chen and G. A. Splitter, Cell. Immunol. 51, 127, 1980), but are tolerant to the thymus-donor genotype. Using such mice to investigate the mechanism(s) of transplantation tolerance, it was found that maintenance of tolerance required active interactions of three subsets of T cells specific for alloantigens of the thymus-donor genotype: (i) Lyt 1+,2- helper T cells, (ii) Lyt 1-,2+ suppressor T cells, and (iii) Lyt 1+,2-,Qa 1.2+ suppressor-inducer T cells. In mixed-lymphocyte culture, helper T cells could be activated by alloantigens of the thymus-donor genotype, but clonal expansion of these helper T cells was inhibited by suppressor T cells with the same specificity. Furthermore, exogenous interleukin-2 (IL-2) could modulate this suppressor activity, which suggested that one consequence of suppression was to limit IL-2 available to effector T cells. The response of cultures to exogenous IL-2 also indicated that thymus alloantigen-specific helper T cells had functional IL-2 receptors. Last, the presence of Lyt 1+,2-,Qa 1.2+ suppressor-inducer T cells were essential for active suppression, as suppressor T cells could not prevent helper T cells from proliferating to thymus-donor alloantigens when Lyt 1+,2-,Qa 1.2+ cells were removed. Altogether, the data presented in this study indicate a feedback-suppression pathway that led to clonal silencing of effector cells in transplantation tolerance.