Angelov Georgi S, Guillaume Philippe, Luescher Immanuel F
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland.
Int Immunol. 2009 Feb;21(2):123-35. doi: 10.1093/intimm/dxn130. Epub 2008 Dec 15.
It has been shown previously that CD8beta in vitro increases the range and the sensitivity of antigen recognition and in vivo plays an important role in the thymic selection of CD8+ T cells. Consistent with this, we report here that CD8+ T cells from CD8beta knockout (KO) P14 TCR transgenic mice proliferate inefficiently in vitro. In contrast to these findings, we also show that CD8beta KO mice mount normal CD8 primary, secondary and memory responses to acute infection with lymphocytic choriomeningitis virus. Tetramer staining and cytotoxic experiments revealed a predominance of CD8-independent CTL in CD8beta KO mice. The TCR repertoire, especially the one of the TCRalpha chain, was different in CD8beta KO mice as compared with B6 mice. Our results indicate that in the absence of CD8beta, CD8-independent TCRs are preferentially selected, which in vivo effectively compensates for the reduced co-receptor function of CD8alphaalpha.
先前的研究表明，体外实验中CD8β可增加抗原识别的范围和敏感性，且在体内对CD8⁺T细胞的胸腺选择起重要作用。与此相符的是，我们在此报告，来自CD8β基因敲除（KO）的P14 TCR转基因小鼠的CD8⁺T细胞在体外增殖效率低下。与这些发现相反，我们还表明，CD8β基因敲除小鼠对淋巴细胞性脉络丛脑膜炎病毒急性感染产生正常的CD8初次、二次和记忆反应。四聚体染色和细胞毒性实验显示，CD8β基因敲除小鼠中主要是不依赖CD8的细胞毒性T淋巴细胞（CTL）。与B6小鼠相比，CD8β基因敲除小鼠的TCR库，尤其是TCRα链的TCR库有所不同。我们的结果表明，在缺乏CD8β的情况下，优先选择不依赖CD8的TCR，这在体内有效地补偿了CD8αα共受体功能的降低。
