Zelenika D, Adams E, Mellor A, Simpson E, Chandler P, Stockinger B, Waldmann H, Cobbold S P
Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford, United Kingdom.
J Immunol. 1998 Aug 15;161(4):1868-74.
We wished to determine whether CD4+ T cells could reject a skin graft that was discordant for a single minor transplantation Ag in the absence of CD8+ T cells or Ab. Transgenic A1(M) mice were constructed that express the rearranged V beta 8.2 and V alpha 10 TCR genes from a T cell clone that is specific for the male Ag (H-Y) in the context of H2-Ek. In addition, the RAG-1(-/-) background was bred onto these mice to eliminate any endogenous TCR rearrangements. As expected, clonal deletion was found to be complete in the thymus of male A1(M) x RAG-1(-/-) mice, while only CD4+ T cells were positively selected and found in the periphery of females. Female A1(M) x RAG-1(-/-) mice were able to rapidly reject (in <14 days) male (but not female) skin grafts in a CD4-dependent fashion. After multiple grafts, it was confirmed that no CD8+ T cells or surface Ig+ B cells were present. An immunofluorescent analysis of spleen cells after grafting showed that the majority of T cells expressed activation markers (CD44, CD25, and intracytoplasmic IL-2) and a significant proportion were making IFN-gamma and IL-4. Surprisingly, the transfer of either Th1 or Th2 CD4+ T cell lines from these mice into T cell-depleted recipients was sufficient to cause a specific rejection of male skin.
我们希望确定在没有CD8⁺ T细胞或抗体的情况下，CD4⁺ T细胞是否能够排斥与单个次要移植抗原不相容的皮肤移植。构建了转基因A1(M)小鼠，其在H2-Ek背景下表达来自对雄性抗原（H-Y）特异的T细胞克隆的重排Vβ8.2和Vα10 TCR基因。此外，将RAG-1(-/-)背景培育到这些小鼠上，以消除任何内源性TCR重排。如预期的那样，在雄性A1(M)×RAG-1(-/-)小鼠的胸腺中发现克隆缺失是完全的，而在雌性小鼠的外周仅发现CD4⁺ T细胞被阳性选择。雌性A1(M)×RAG-1(-/-)小鼠能够以CD4依赖的方式快速排斥（在<14天内）雄性（而非雌性）皮肤移植。多次移植后，证实不存在CD8⁺ T细胞或表面Ig⁺ B细胞。移植后对脾细胞的免疫荧光分析表明，大多数T细胞表达激活标志物（CD44、CD25和胞内IL-2），并且有相当比例的细胞产生IFN-γ和IL-4。令人惊讶的是，将来自这些小鼠的Th1或Th2 CD4⁺ T细胞系转移到T细胞耗竭的受体中足以引起对雄性皮肤的特异性排斥。
