A negative regulatory function of B7 revealed in B7-1 transgenic mice.

A negative regulatory function of B7 revealed in B7-1 transgenic mice.
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B7-1 转基因小鼠中揭示了 B7 的负调节功能。

DOI:
10.1016/1074-7613(94)90072-8
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发表时间:
1994
期刊:
影响因子:
32.4
通讯作者:
Freeman,GJ
Freeman,GJ
中科院分区:
医学1区
文献类型:
--
作者:
Sethna,MP;vanParijs,L;Sharpe,AH;Abbas,AK;Freeman,GJ

文献摘要

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为了分析T细胞共刺激分子在体内的功能,我们构建了一个在成熟B细胞上组成型表达鼠87- 1的转基因小鼠品系。在87- 1转基因小鼠中,对T依赖性半抗原蛋白缀合物的抗体应答和血清免疫球蛋白水平显著降低。这种免疫缺陷不是由于固有的B细胞缺陷,因为对T-非依赖性半抗原缀合物的抗体应答是正常的。此外,用抗B7 -1治疗恢复了转基因小鼠应答半抗原-蛋白质缀合物的能力,证明缺陷的抗体应答直接归因于87-1的表达。这些结果表明,共刺激分子如87- 1的时间调节表达可能有助于启动或下调(反馈抑制)的T依赖性免疫反应在体内,和抑制功能是占主导地位的转基因小鼠组成性表达高水平的这种共刺激分子。
To analyze the functions of T cell costimulators in vivo, we have constructed a transgenic mouse strain that constitutively expresses murine 87-l on mature B cells. Antibody responses to T-dependent haptenprotein conjugates and serum immunoglobulln levels are markedly depressed in 87-l transgenic mice. This immune deficiency is not due to an intrinsic B cell defect, as antibody responses to T-independent hapten conjugates are normal. Furthermore, treatment with anti-B7-1 restores the capacity of transgenic mice to respond to hapten-protein conjugates, demonstrating that the deficient antibody responses are directly attributable to the expression of 87-1. These results suggest that the temporally regulated expression of costimulators such as 87-l may contribute to either initiation or down-regulation(feedback inhibition) of Tdependent immune responses in vivo, and that the inhibitory function is dominant in transgenic mice that constitutively express high levels of this costimulator.