The effects of B7-dependent costimulation on T cell division and survival in vivo and in vitro are dependent on antigen concentration
The effects of B7-dependent costimulation on T cell division and survival in vivo and in vitro are dependent on antigen concentration
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DOI：
10.1002/eji.200323929
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发表时间：
2003-08-01
影响因子：
5.4
通讯作者：
Ronchese, F
中科院分区：
文献类型：
--
作者：
Lumsden, JM;Prasad, SJ;Ronchese, F
我们使用5-（和6-）羧基荧光素二乙酸琥珀酰亚胺酯标记的TCR转基因CD 4（+）T细胞来研究B7共刺激对T细胞活化和克隆扩增的贡献。用融合蛋白细胞毒性T淋巴细胞相关抗原4（CTLA 4）-IG阻断B7共刺激，其阻止B7与T细胞上其受体CD 28的相互作用。CTLA 4-IG对T细胞抗原（Ag）/MHC配体浓度的影响不同。在CTLA 4-IG存在的情况下，T细胞在体外进行细胞分裂需要高出十倍的Ag浓度。在高Ag浓度下，无论是否存在CTLA 4-IG，T细胞分裂都以相当的速率发生;然而，T细胞存活和克隆扩增被强烈抑制。IL-2的加入恢复了T细胞的存活，但对低剂量的Ag没有反应性。在体内，B7共刺激同样需要的生存Ag特异性T细胞，但不为细胞分裂，在高量的Ag。因此，B7共刺激调节CD 4（+）T细胞的反应，通过促进细胞分裂，在有限数量的Ag的存在下，并通过保护T细胞从凋亡的开始。
We used 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester-labeled TCR-transgenic CD4(+) T cells to investigate the contribution of B7 costimulation to T cell activation and clonal expansion. B7 costimulation was blocked with the fusion protein cytotoxic T lymphocyte-associated antigen-4 (CTLA4)-Ig, which prevents the interaction of B7 with its receptor CD28 on T cells. CTLA4-Ig had different effects depending on the density of antigen (Ag)/MHC ligands available by T cells. In the presence of CTLA4-Ig, tenfold higher concentrations of Ag were required for T cells to undergo cell division in vitro. At high Ag concentrations, T cell division occurred at comparable rates whether in the presence or absence of CTLA4-Ig; however, T cell survival and clonal expansion were strongly inhibited. Addition of IL-2 restored T cell survival but not responsiveness to low doses of Ag. In vivo, B7 costimulation was similarly required for the survival of Ag-specific T cells but not for cell division in response to high amounts of Ag. Thus, B7 costimulation regulates CD4(+) T cell responses by promoting cell division in the presence of limiting amounts of Ag, and by protecting T cells from the onset of apoptosis.