Transplantation tolerance: Lyt-1+2- helper T cells require a second proliferation signal to overcome Lyt- 1-2+ suppressor T cell activity.

This study investigated why nude mouse T cell precursors that differentiated in an allogeneic thymus graft were rendered tolerant to alloantigens of the thymus genotype. Our results showed that Lyt- 1-,2+ suppressor T cells inhibited clonal expansion of helper T cells reactive to thymus-donor alloantigens as the mechanism of tolerance. This suppressor T cell activity could be modulated in vitro with either exogenous interleukin 2 (IL 2) or anti-Lyt-1 monoclonal antibody as an IL 2 inducer. Monoclonal antibody stimulation of IL 2 production by primed helper T cells was effective even in the presence of suppressor T cells. These results indicate: i) that alloantigen-specific helper T cells were not defective in their ability to recognize alloantigens of the thymus-donor genotype and to produce IL 2; ii) that Lyt-1-,2+ suppressor T cells prevented Lyt-1+,2- helper T cells specific for the thymus-donor alloantigens from producing IL 2; and iii) that signals delivered through binding of anti-Lyt-1 antibody modulated suppressor activity on alloantigen-primed helper T cells and permitted IL 2 production by these helper T cells. Accordingly, a delicate balance of helper and suppressor T cell activity was required for the maintenance of transplantation tolerance. Furthermore, these results argue against clonal deletion of Lyt-1+,2- helper T cells reactive to alloantigens of the thymic genotype as a mechanism of such transplantation tolerance.