CD28 costimulation independence of target organ versus circulating memory antigen-specific CD4+ T cells
CD28 costimulation independence of target organ versus circulating memory antigen-specific CD4+ T cells
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DOI：
10.1172/jci200318317
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发表时间：
2003-09-01
影响因子：
15.9
通讯作者：
Kotzin, BL
中科院分区：
文献类型：
--
作者：
Fontenot, AP;Gharavi, L;Kotzin, BL
T细胞受体与CD 28共刺激的结合通常是幼稚T细胞活化所需的，而记忆细胞的再活化较少依赖于CD 28共刺激。我们在慢性铍病中研究了这一过程，其中肺部抗原特异性CD 4（+）T细胞的频率很大，并且循环抗原特异性细胞也可检测到。在肺中，大部分CD 4（+）T细胞停止表达CD 28 mRNA和蛋白，这种表型变化与肺部炎症相关。在存在抑制CD 28-B7相互作用的CTLA-4 Ig浓度的情况下，肺中铍特异性CD 4（+）T细胞仍然能够增殖并分泌IFN-γ以响应培养中的铍。这种CD 28共刺激的功能独立性包括肺CD 28（+）效应细胞。尽管肺CD 4（+）CD 28（-）细胞保留了分泌Th 1型细胞因子的能力以响应铍，但与CD 28（+）T细胞相比，它们显示出较低的增殖能力，并且更容易发生细胞死亡。与肺细胞相反，CD 28-B7相互作用的抑制显着降低了血液中铍特异性T细胞的反应。总之，这些发现表明记忆性CD 4（+）T细胞从中央记忆细胞中的CD 28依赖性转变为功能独立性，然后在效应细胞中失去CD 28表达。
T cell receptor engagement with CD28 costimulation is generally required for naive T cell activation, whereas reactivation of memory cells is less dependent on CD28 costimulation. We studied this process in chronic beryllium disease, in which the frequency of antigen-specific CD4(+) T cells in the lung is large and circulating antigen-specific cells are also detectable. In the lung, a large fraction of CD4(+)T cells stopped expressing CD28 mRNA and protein, and this change in phenotype correlated with lung inflammation. In the presence of concentrations of CTLA-4Ig that inhibited the CD28-B7 interaction, beryllium-specific CD4(+) T cells in lung were still able to proliferate and secrete IFN-gamma in response to beryllium in culture. This functional independence of CD28 costimulation included lung CD28(+) effector cells. Although lung CD4(+)CD28(-) cells retained the ability to secrete Th1-type cytokines in response to beryllium, they showed less proliferative capacity and were more susceptible to cell death compared with CD28(+) T cells. In contrast to lung cells, inhibition of the CD28-B7 interaction markedly reduced responses of beryllium-specific T cells in blood. Taken together, these findings suggest transition within memory CD4(+) T cells from CD28 dependence in central memory cells to functional independence and then loss of CD28 expression in effector cells.