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.
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D005838:Genotype; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D007518:Isoantibodies / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008806:Mice, Inbred AKR; D008819:Mice, Nude; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000637:transplantation*
D000950:Antigens, Ly; D006183:H-2 Antigens; D007376:Interleukin-2; D007518:Isoantibodies; C029805:Lyt antibodies