Chen B P, Splitter G A
J Immunol. 1983 Jul;131(1):57-63.
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.
本研究调查了在同种异体胸腺移植中分化的裸鼠T细胞前体为何对胸腺基因型的同种异体抗原产生耐受。我们的结果表明，Lyt-1-、2+抑制性T细胞抑制对胸腺供体同种异体抗原产生反应的辅助性T细胞的克隆扩增，以此作为耐受机制。这种抑制性T细胞活性可用外源性白细胞介素2（IL-2）或作为IL-2诱导剂的抗Lyt-1单克隆抗体在体外进行调节。即使存在抑制性T细胞，用单克隆抗体刺激经致敏的辅助性T细胞产生IL-2也是有效的。这些结果表明：i）同种异体抗原特异性辅助性T细胞在识别胸腺供体基因型的同种异体抗原和产生IL-2的能力方面并无缺陷；ii）Lyt-1-、2+抑制性T细胞阻止对胸腺供体同种异体抗原具有特异性的Lyt-1+、2-辅助性T细胞产生IL-2；iii）通过抗Lyt-1抗体结合传递的信号调节对同种异体抗原致敏的辅助性T细胞的抑制活性，并使这些辅助性T细胞能够产生IL-2。因此，维持移植耐受需要辅助性和抑制性T细胞活性的微妙平衡。此外，这些结果反对将对胸腺基因型同种异体抗原产生反应的Lyt-1+、2-辅助性T细胞的克隆清除作为这种移植耐受的一种机制。
