Picus J, Holley K, Aldrich W R, Griffin J D, Letvin N L
J Exp Med. 1985 Dec 1;162(6):2035-52. doi: 10.1084/jem.162.6.2035.
Restriction on cytolytic T lymphocyte (CTL)-target cell-interactions are studied in the primate S. oedipus, a naturally occurring A + B----A bone marrow-chimeric species. We show that the T cell, B cell, and myelomonocytic progenitor cell populations are chimeric in this species. We selected animals for study that are populated by fully major histocompatibility complex (MHC)-disparate hematopoietic cell populations, using a functional assay system. We then developed an in vitro system for analyzing at the clonal level the genetic restrictions on the trinitrophenyl-specific CTL-target cell interactions of this species. In this system, we have shown that tolerance to foreign MHC determinants was not, of itself, sufficient to facilitate the generation of CTL specific for target cells expressing those foreign MHC determinants. Rather, a marked preference for the expansion of CTL clones with a restriction for target cells bearing the host animals' MHC determinants was seen. Hematopoietically derived cells did not affect the repertoire of these T lymphocytes. These studies represent the first demonstration of the phenomenon of an environment dictating interactional restrictions on CTL in a naturally occurring bone marrow-chimeric animal. This is also the first demonstration of the profound influence of the environment on the repertoire of the T lymphocyte in a primate species.
在灵长类动物眼斑食蟹猴(一种自然存在的A + B----A骨髓嵌合物种)中研究了细胞溶解性T淋巴细胞(CTL)与靶细胞相互作用的限制。我们发现该物种的T细胞、B细胞和骨髓单核细胞祖细胞群体是嵌合的。我们使用功能测定系统选择了由完全主要组织相容性复合体(MHC)不同的造血细胞群体组成的动物进行研究。然后,我们开发了一种体外系统,用于在克隆水平分析该物种三硝基苯基特异性CTL与靶细胞相互作用的遗传限制。在这个系统中,我们发现对异源MHC决定簇的耐受性本身并不足以促进针对表达这些异源MHC决定簇的靶细胞产生CTL。相反,我们观察到明显倾向于扩增对携带宿主动物MHC决定簇的靶细胞具有限制性的CTL克隆。造血来源的细胞并不影响这些T淋巴细胞的库。这些研究首次证明了在自然发生的骨髓嵌合动物中环境决定CTL相互作用限制这一现象。这也是首次证明环境对灵长类物种T淋巴细胞库有深远影响。