Thomas D W, Shevach E M
Proc Natl Acad Sci U S A. 1977 May;74(5):2104-8. doi: 10.1073/pnas.74.5.2104.
Alloreactive guinea pig thymus-derived (T) cells generated in vitro were rendered unresponsive to allogeneic macrophages by treatment with bromodeoxyuridine and light. The remaining T cells were subsequently primed and rechallenged in tissue culture with trinitrophenyl (Tnp)-modified syngeneic or allogeneic macrophages. By this procedure we found that the remaining T cells primed with Tnp-modified allogeneic macrophages could be restimulated only with Tnp-modified allogeneic, not syngeneic, macrophages. Similarily, if the remaining T cells were primed with Tnp-modified syngeneic macrophages, they could be restimulated only by Tnp-modified syngeneic, and not by allogeneic, macrophages. In contrast, no T cell sensitization with Tnp-modified syngeneic or allogeneic macrophages occurred if the alloreactive T cells were treated with light alone, suggesting that an uninhibited mixed leukocyte reaction causes nonspecific suppression of antigen-specific T cell priming. These results indicate that the genetic restriction of T cell-macrophage interactions is imposed by the type of macrophage used for initial sensitization rather than by a requirement for self-recognition through cellular interaction structures.
体外产生的同种异体反应性豚鼠胸腺来源(T)细胞,通过用溴脱氧尿苷和光照处理,使其对同种异体巨噬细胞无反应。剩余的T细胞随后在组织培养中用三硝基苯基(Tnp)修饰的同基因或同种异体巨噬细胞进行初次致敏和再次刺激。通过这个过程,我们发现用Tnp修饰的同种异体巨噬细胞初次致敏的剩余T细胞,只能被Tnp修饰的同种异体巨噬细胞,而不是同基因巨噬细胞再次刺激。同样,如果剩余的T细胞用Tnp修饰的同基因巨噬细胞初次致敏,它们只能被Tnp修饰的同基因巨噬细胞,而不是同种异体巨噬细胞再次刺激。相比之下,如果同种异体反应性T细胞仅接受光照处理,则不会发生用Tnp修饰的同基因或同种异体巨噬细胞进行的T细胞致敏,这表明不受抑制的混合淋巴细胞反应会导致抗原特异性T细胞初次致敏的非特异性抑制。这些结果表明,T细胞 - 巨噬细胞相互作用的遗传限制是由用于初次致敏的巨噬细胞类型施加的,而不是通过细胞相互作用结构进行自我识别的要求。