Naive CD28-deficient T cells can initiate but not sustain an in vitro antigen-specific immune response.

Naive CD28-deficient T cells can initiate but not sustain an in vitro antigen-specific immune response.
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原始 CD28 缺陷 T 细胞可以启动但不能维持体外抗原特异性免疫反应。

DOI:
10.4049/jimmunol.154.11.5757
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发表时间:
1995
影响因子:
4.4
通讯作者:
D. Loh
D. Loh
中科院分区:
医学2区
文献类型:
--
作者:
P. Lucas;I. Negishi;K. Nakayama;L. E. Fields;D. Loh

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初始T细胞需要Ag特异性信号,以及共刺激信号以产生初级Ag特异性应答。由于它们的低前体频率,一直难以研究这些Ag特异性T细胞的共刺激需求。我们已经产生了一个CD 28缺陷的小鼠,已经繁殖到TCR转基因(Tg)小鼠,以更好地研究CD 28在CD 4 + T细胞对Ag的反应过程中的功能。在不存在CD 28的情况下,幼稚TCR Tg T细胞对肽反应强烈,但对促分裂原活化反应差。比较活化诱导的细胞表面分子,包括CD 25,CD 44,CD 69和CD 71,显示在Ag刺激后的前24至48小时内,CD 28+和CD 28- TCR Tg T细胞之间没有显著差异。尽管相对正常的表面表型和正常的增殖反应的Ag,CD 28- T细胞产生很少的IL-2,有较低的Ag浓度的敏感性降低,并不能维持其增殖反应。这些结果表明,幼稚T细胞能够利用其他共刺激信号来启动初级Ag特异性应答,但需要CD 28来实现最佳的持续增殖。
Naive T cells require an Ag-specific signal, as well as a costimulatory signal to mount a primary Ag-specific response. Because of their low precursor frequency, it has been difficult to study costimulatory requirements of these Ag-specific T cells. We have generated a CD28-deficient mouse that has been bred to a TCR transgenic (Tg) mouse to better study the function of CD28 during CD4+ T cell responses to Ag. In the absence of CD28, naive TCR Tg T cells responded vigorously to peptide, but responded poorly to mitogen activation. Comparison of activation-induced cell-surface molecules, including CD25, CD44, CD69, and CD71, showed no significant differences between CD28+ and CD28- TCR Tg T cells during the first 24 to 48 h after Ag stimulation. Despite relatively normal surface phenotype and normal proliferative response to Ag, CD28- T cells produced little IL-2, had a decreased sensitivity to lower Ag concentrations, and were unable to maintain their proliferative response. These results suggest that naive T cells are able to utilize other costimulatory signals to initiate a primary Ag-specific response, but require CD28 for optimal, sustained proliferation.