Walunas T L, Sperling A I, Khattri R, Thompson C B, Bluestone J A
Ben May Institute, University of Chicago, IL 60637, USA.
J Immunol. 1996 Feb 1;156(3):1006-13.
Thymocyte development requires positive selection of clones that can recognize Ag presented by MHC molecules and negative selection of clones that are self-reactive. However, the costimulatory signals required for negative selection and cell death, or positive selection and the transition to the peripheral lymphoid system, are not well understood. Many molecular interactions that are important for T cell activation have also been found to play a role in thymocyte development. The importance of the CD28/B7 interaction in the activation of mature T cells and recent observations that CD28 may play a role negative selection of developing CD4+CD8+ thymocytes suggest that CD28 may also be involved in development and maintenance of T cell tolerance. CD28-deficient mice were crossed to alpha beta and gamma delta TCR transgenic as well as H-2k Mlsc-bearing animals and were used to address the role of CD28 in positive and negative selection of developing T cells. The CD28-deficient animals demonstrated no obvious deficiency in either positive or negative selection of developing thymocytes. However, when mixed bone marrow chimeras were created with cells derived from both CD28-deficient and wild-type mice, the CD28+ T cells had a selective advantage over the CD28-deficient T cells. Therefore, it appears that CD28, although not essential for the selection of T cells during development, may allow for additional signals that increase the efficiency of selection and/or expansion of peripheral T cell populations.
胸腺细胞的发育需要对能够识别由MHC分子呈递的抗原的克隆进行阳性选择，以及对自身反应性克隆进行阴性选择。然而，阴性选择和细胞死亡所需的共刺激信号，或阳性选择以及向外周淋巴系统的转变，目前还没有得到很好的理解。许多对T细胞活化很重要的分子相互作用也被发现参与了胸腺细胞的发育。CD28/B7相互作用在成熟T细胞活化中的重要性，以及最近观察到CD28可能在发育中的CD4+CD8+胸腺细胞的阴性选择中发挥作用，这表明CD28也可能参与T细胞耐受性的发育和维持。将CD28缺陷小鼠与αβ和γδTCR转基因小鼠以及携带H-2k Mlsc的动物进行杂交，并用于研究CD28在发育中T细胞的阳性和阴性选择中的作用。CD28缺陷动物在发育中胸腺细胞的阳性或阴性选择方面均未表现出明显缺陷。然而，当用来自CD28缺陷小鼠和野生型小鼠的细胞创建混合骨髓嵌合体时，CD28+T细胞比CD28缺陷T细胞具有选择性优势。因此，似乎CD28虽然在发育过程中对T细胞的选择不是必需的，但可能允许额外的信号增加外周T细胞群体的选择效率和/或扩增。
