van den Bogaerde J, Howard J C
Department of Immunology, Institute of Animal Physiology and Genetics, Babraham, Cambridge, UK.
Int Immunol. 1991 Jan;3(1):49-56. doi: 10.1093/intimm/3.1.49.
We have investigated the ability of Syrian hamster lymphocytes to generate cytotoxic responses against classical MHC molecules on xenogeneic cells. Our data show that hamster lymph node cells can be stimulated in an in vitro primary mixed lymphocyte culture by irradiated rat or mouse lymphoid cells to produce a substantial cytotoxic response assayed on 51Cr-labelled xenogeneic blasts. Using congenic recombinant rat and mouse targets, the specificity of the cytotoxic activity could be localized to genetic regions known to determine classical class I histocompatibility antigens in these two species. In addition, specific cytotoxicity could be demonstrated on transfectant target cells expressing only the relevant rat class I molecules, and specific cytotoxicity could be inhibited by a monoclonal antibody specific for a rat classical class I molecule. Elimination of B cells did not affect the ability of the responder population to generate xenogeneic cytotoxicity. In further experiments it was shown that hamster xenogeneic killers could distinguish between two subtly modified forms of a rat classical class I molecule essentially as efficiently as can allogeneic rat killers. Finally, lymph node cells from female hamsters primed in vivo with male hamster cells were able to generate weak but significant male-specific cytotoxicity after boosting in vitro. In sum, our experiments show that the general outline of the cytotoxic T cell repertoire of the Syrian hamster is conventional. These results suggest that monomorphic class I molecules expressed by the Syrian hamster probably function normally to direct the differentiation of its cytotoxic T cell repertoire.
我们研究了叙利亚仓鼠淋巴细胞对异种细胞上经典MHC分子产生细胞毒性反应的能力。我们的数据表明,在体外初次混合淋巴细胞培养中,仓鼠淋巴结细胞可被经辐照的大鼠或小鼠淋巴细胞刺激,从而对51Cr标记的异种胚细胞进行检测时产生显著的细胞毒性反应。使用同基因重组大鼠和小鼠靶细胞,细胞毒性活性的特异性可定位到已知决定这两个物种中经典I类组织相容性抗原的遗传区域。此外,在仅表达相关大鼠I类分子的转染靶细胞上可证明特异性细胞毒性,并且特异性细胞毒性可被针对大鼠经典I类分子的单克隆抗体抑制。去除B细胞并不影响反应细胞群体产生异种细胞毒性的能力。在进一步的实验中表明,仓鼠异种杀伤细胞区分大鼠经典I类分子的两种细微修饰形式的效率基本上与同种异体大鼠杀伤细胞相同。最后,体内用雄性仓鼠细胞致敏的雌性仓鼠的淋巴结细胞在体外增强后能够产生微弱但显著的雄性特异性细胞毒性。总之,我们的实验表明叙利亚仓鼠细胞毒性T细胞库的总体概况是常规的。这些结果表明,叙利亚仓鼠表达的单态I类分子可能正常发挥作用,指导其细胞毒性T细胞库的分化。