Longo D L, Kruisbeek A M, Davis M L, Matis L A
Proc Natl Acad Sci U S A. 1985 Sep;82(17):5900-4. doi: 10.1073/pnas.82.17.5900.
We previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. We now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus.
我们先前已经证明，在辐射诱导的骨髓嵌合体中，T细胞自身Ia限制特异性似乎与T细胞发育过程中胸腺内骨髓来源的抗原呈递（或树突状）细胞的表型相关。然而，由于过去通过成年胸腺移植直接检测胸腺功能一直未成功，这些相关性必然是间接的。我们现在报告，通过用抗胸腺细胞球蛋白和可的松处理胸腺供体，获得了尺寸减小的成年胸腺移植到裸鼠体内后成功获得功能性T细胞。当将亲代B10.D2（I-Ad）胸腺皮下移植到（B10 Scn×B10.D2）F1裸鼠（I-Ab,d）中时，它们的T细胞被限制于与I-Ad基因产物而非I-Ab基因产物相关的抗原识别。此外，在辐射后6个月或更长时间（此时抗原呈递细胞功能为供体骨髓表型）移植到（B10×B10.D2）F1裸鼠体内的（B10×B10.D2）F1（I-Ab,d）----B10（I-Ab）嵌合体的胸腺产生的T细胞被限制于与I-Ad和I-Ab基因产物相关的抗原识别。完全异基因骨髓嵌合体的胸腺似乎产生具有骨髓供体和胸腺宿主限制特异性的T细胞。因此，当胸腺供体是辐射诱导的骨髓嵌合体时，裸鼠受体的T细胞I区限制至少部分由嵌合胸腺中骨髓来源的胸腺抗原呈递细胞或树突状细胞的表型决定。
