Zinkernagel R M, Callahan G N, Althage A, Cooper S, Streilein J W, Klein J
J Exp Med. 1978 Mar 1;147(3):897-911. doi: 10.1084/jem.147.3.897.
The thymus determines the spectrum of the receptor specificities of differentiating T cells for self-H-2; however, the phenotypic expression of T cell's specificity for self plus virus is determined predominantly by the H-2 type of the antigen presenting cells of the peripheral lymphoreticular system. Furthermore, virus specific helper T cells are essential for the generation of virus-specific cytotoxic T cells. For cooperation between mature T cells and other lymphocytes to be functional in chimeras, thymic epithelial cells and lymphohemopoietic stem cells must share the I region; killer T-cell generation also requires in addition compatibility for at least one K or D region. These conclusions derive from the following experiments: A leads to (A X B)F1 chimeric lymphocytes do produce virus-specific cytotoxic T-cell activity for infected A but not for infected B cells; when sensitized in an acutely irradiated and infected recipient (A X B)F1 these chimeric lymphocytes respond to both infected A and B. Therefore the predominantly immunogenically infected cells of chimeras the radiosensitive and by donor stem cells replaced lymphoreticular cells. In this adoptive priming model (KAIA/DB leads to KAIA/DC) chimeric lymphocytes could be sensitized in irradiated and infected F1 against KA and DC but not against infected DB targets. In contrast KBIB/DA leads to KCIC/DA chimeras' lymphocytes could not be sensitized at all in appropriately irradiated and infected F1 recipients. Thus these latter chimeras probably lack functional I-specific T helper cells that are essential for the generation of T killer cells against infected D compatible targets. If T cells learn in the thymus to recognize H-21 or K, D markers that are not at least partially carried themselves in other cells of the lymphoreticular system immunological interactions will be impossible and this paradox situation results in phenotypic immune incompetence in vivo.
胸腺决定分化中的T细胞对自身H-2受体特异性的范围；然而，T细胞对自身加病毒特异性的表型表达主要由外周淋巴网状系统的抗原呈递细胞的H-2类型决定。此外，病毒特异性辅助性T细胞对于病毒特异性细胞毒性T细胞的产生至关重要。为了使成熟T细胞与其他淋巴细胞之间的合作在嵌合体中发挥功能，胸腺上皮细胞和淋巴细胞造血干细胞必须共享I区；杀伤性T细胞的产生还另外需要至少一个K或D区的相容性。这些结论来自以下实验：A导致（A×B）F1嵌合淋巴细胞确实对感染的A产生病毒特异性细胞毒性T细胞活性，但对感染的B细胞则不产生；当在急性照射并感染的受体（A×B）F1中致敏时，这些嵌合淋巴细胞对感染的A和B都有反应。因此，嵌合体中主要被免疫原性感染的细胞是对辐射敏感且由供体干细胞替代的淋巴网状细胞。在这种过继致敏模型（KAIA/DB导致KAIA/DC）中，嵌合淋巴细胞可在照射并感染的F1中针对KA和DC致敏，但不能针对感染的DB靶标致敏。相比之下，KBIB/DA导致KCIC/DA嵌合体的淋巴细胞在适当照射并感染的F1受体中根本无法致敏。因此，这些后者的嵌合体可能缺乏功能性I特异性T辅助细胞，而这些细胞对于产生针对感染的D相容靶标的T杀伤细胞至关重要。如果T细胞在胸腺中学习识别H-2I或K、D标记，而这些标记在淋巴网状系统的其他细胞中至少没有部分自身携带，那么免疫相互作用将是不可能的，这种矛盾的情况会导致体内表型免疫无反应性。
