CD28 is an inducible T cell surface antigen that transduces a proliferative signal in CD3+ mature thymocytes.
CD28 is an inducible T cell surface antigen that transduces a proliferative signal in CD3+ mature thymocytes.
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DOI：
10.4049/jimmunol.144.5.1646
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发表时间：
1990-03
影响因子：
4.4
通讯作者：
Laurence A. Turka;J. Ledbetter;Kelvin P. Lee;C. June;C. Thompson
中科院分区：
文献类型：
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作者：
Laurence A. Turka;J. Ledbetter;Kelvin P. Lee;C. June;C. Thompson
在胸腺个体发育期间TCR基因的重排产生T细胞特异性的库，其被细化以确保自身反应性克隆的缺失和T细胞应答的MHC限制。通过辅助分子CD 2、CD 4和CD 8传递的信号在T细胞分化的这一阶段中起着至关重要的作用。最近，CD 28已被鉴定为大多数成熟T细胞表面的信号转导分子。CD 28分子的扰动刺激T细胞活化的新途径，调节包括IL-2在内的多种淋巴因子的产生。我们研究了CD 28在胸腺个体发育过程中的表达和功能，以及在静息和活化PBL中的表达和功能。静息胸腺细胞中CD 28+细胞的百分比可变（3 - 25%，n = 8），但仅在成熟的CD 3+（亮）CD 4/CD 8细胞中发现高密度。未分离的胸腺细胞和分离的CD 3-CD 28-/dull细胞在PMA + IL-2或PMA+离子霉素刺激下均增殖。PMA处理还快速上调了CD 3-亚群中的CD 28表达，因为这些细胞变成了CD 3-CD 28+（亮）。尽管PMA能够诱导CD 3-细胞中高密度的CD 28表达，但与未分离的细胞相比，CD 3-胸腺细胞对PMA+抗CD 28 mAb没有增殖反应。用固定化抗CD 3 mAb刺激的CD 3+胸腺细胞也未能在培养物中增殖。然而，添加IL-2或抗CD 28 mAb均支持增殖，表明仅CD 3+细胞可响应CD 28信号传导。抗-CD 3和抗-CD 28 mAb的共致效应是IL-2依赖性的，因为它被抗-IL-2 R mAb消除。有趣的是，CD 3+细胞的细胞表面上的CD 28的表达也是可诱导的，因为流式细胞术分析表明，在CD 3+胸腺细胞和外周血T细胞的抗CD 3刺激后24至48小时，细胞表面CD 28增加了10倍。这种增加是由于CD 28 mRNA水平的相应增加。总之，这些结果表明，CD 28是在CD 3-和CD 3+细胞中的诱导型T细胞抗原。此外，CD 28通路的刺激可以提供第二个信号，以支持通过TCR/CD 3复合物刺激的CD 3+胸腺细胞的生长，因此可能代表胸腺个体发育期间的阳性选择机制。
The rearrangement of TCR genes during thymic ontogeny creates a repertoire of T cell specificities that is refined to ensure the deletion of autoreactive clones and the MHC restriction of T cell responses. Signals delivered via the accessory molecules CD2, CD4, and CD8 have a crucial role in this phase of T cell differentiation. Recently, CD28 has been identified as a signal transducing molecule on the surface of most mature T cells. Perturbation of the CD28 molecule stimulates a novel pathway of T cell activation regulating the production of a variety of lymphokines including IL-2. We have studied the expression and function of CD28 during thymic ontogeny, and in resting and activated PBL. A variable percentage of resting thymocytes were CD28+ (3 to 25%, n = 8), but it was found in high density only on mature CD3+(bright) CD4/CD8 cells. Both unseparated thymocytes and isolated CD3-CD28-/dull cells proliferated when stimulated with PMA plus IL-2 or PMA plus ionomycin. PMA treatment also rapidly up-regulated CD28 expression in the CD3- subset as these cells became CD3-CD28+(bright). Despite the ability of PMA to induce high density CD28 expression in CD3- cells, CD3- thymocytes did not proliferate in response to PMA plus anti-CD28 mAb, in contrast to unseparated cells. CD3+ thymocytes stimulated with immobilized anti-CD3 mAb also failed to proliferate in culture. However, the addition of either IL-2 or anti-CD28 mAb supported proliferation, suggesting that only CD3+ cells could respond to CD28 signaling. The comitogenic effect of anti-CD3 and anti-CD28 mAb was IL-2 dependent as it was abrogated by an anti-IL-2R mAb. Interestingly, the expression of CD28 on the cell surface of CD3+ cells was also inducible, as flow cytometric analysis demonstrated a 10-fold increase in cell surface CD28 by 24 to 48 h after anti-CD3 stimulation of both CD3+ thymocytes and peripheral blood T cells. This increase was accounted for by a commensurate increase in CD28 mRNA levels. Together, these results suggest that CD28 is an inducible T cell antigen in both CD3- and CD3+ cells. In addition, stimulation of the CD28 pathway can provide a second signal to support the growth of CD3+ thymocytes stimulated through the TCR/CD3 complex, and may therefore represent a mechanism for positive selection during thymic ontogeny.