Fields P E, Finch R J, Gray G S, Zollner R, Thomas J L, Sturmhoefel K, Lee K, Wolf S, Gajewski T F, Fitch F W
Department of Pathology, University of Chicago, IL 60637, USA.
J Immunol. 1998 Nov 15;161(10):5268-75.
Using a TCR transgenic mouse bred onto a recombinase-activating gene-2-deficient background, we have examined the influence of B7.1 and B7.2 on activation of naive, CD8+ T cells in vitro. We found that B7.1 was a more potent costimulus than B7.2 for induction of proliferation and IL-2 production by naive CD8+ T cells. This difference appeared to be quantitative in nature, as determined using transfectants expressing various defined levels of B7.1 or B7.2, or using purified B7.1 or B7.2 fusion proteins. In contrast to the quantitative differences seen in stimulation of naive T cells, B7.1 and B7.2 were comparable in their ability to costimulate responses in T cells previously primed in vitro. In addition, primed, but not naive, T cells were capable of proliferating and producing IL-2 in response to a TCR stimulus alone, apparently in the absence of B7 costimulation. Lastly, we found that B7.1 and B7.2 were equivalently capable of driving differentiation of naive CD8+ T cells into an IL-4-producing phenotype when exogenous IL-4 was added to the primary culture or to an IFN-gamma-producing phenotype in the presence of IL-12. These results indicate that signals generated by B7.1 and B7.2 are qualitatively similar, but that B7.1 is quantitatively stronger than B7.2. Further, our results indicate that the activation state of the responding T cell may influence the efficiency with which the T cell can respond to a costimulatory signal provided by either B7.1 or B7.2.
我们利用培育在重组酶激活基因-2缺陷背景上的TCR转基因小鼠,在体外研究了B7.1和B7.2对初始CD8⁺ T细胞激活的影响。我们发现,对于初始CD8⁺ T细胞的增殖诱导和IL-2产生,B7.1作为共刺激分子比B7.2更有效。使用表达不同定义水平的B7.1或B7.2的转染子,或使用纯化的B7.1或B7.2融合蛋白确定,这种差异在本质上似乎是定量的。与在初始T细胞刺激中看到的定量差异相反,B7.1和B7.2在共刺激先前在体外致敏的T细胞反应的能力方面相当。此外,致敏但非初始的T细胞能够仅对TCR刺激作出增殖反应并产生IL-2,显然在没有B7共刺激的情况下也是如此。最后,我们发现,当在原代培养物中添加外源性IL-4时,或在存在IL-12的情况下,B7.1和B7.2同样能够驱动初始CD8⁺ T细胞分化为产生IL-4的表型或分化为产生IFN-γ的表型。这些结果表明,B7.1和B7.2产生的信号在质量上相似,但B7.1在数量上比B7.2更强。此外,我们的结果表明,反应性T细胞的激活状态可能影响T细胞对由B7.1或B7.2提供的共刺激信号作出反应的效率。