Teh S J, Killeen N, Tarakhovsky A, Littman D R, Teh H S
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Blood. 1997 Feb 15;89(4):1308-18.
The CD2 glycoprotein has been implicated in both positive and negative regulation of T-cell mitogenesis. To study the involvement of CD2 in T-lymphocyte development and immune responses, we have analyzed two lines of CD2-null mice, each expressing a distinct class I major histocompatibility complex (MHC)-restricted T-cell receptor (TCR). In both situations, the absence of CD2 appeared to promote the positive selection of cells in a manner that is similar to that which occurs in the absence of CD5. Consistent with this, compound homozygotes that lacked both CD2 and CD5 showed evidence of enhanced positive selection even in the absence of a transgenic TCR. Despite the observed enhancement of positive selection, the lack of CD2 was associated with defects in proliferative responses and interferon-gamma production when transgenic thymocytes and mature T lymphocytes were stimulated with the appropriate antigens. These findings raise the possibility that impaired sensitivity to selecting ligands in the thymus may provide a selective advantage that improves the efficiency of positive selection for certain TCRs. Furthermore, the results highlight the potential for a differential role for CD2 in thymocyte selection and T-cell immune responses.
CD2糖蛋白与T细胞有丝分裂的正调控和负调控均有关联。为了研究CD2在T淋巴细胞发育和免疫反应中的作用，我们分析了两系CD2基因敲除小鼠，每一系均表达一种独特的I类主要组织相容性复合体（MHC）限制性T细胞受体（TCR）。在这两种情况下，CD2的缺失似乎以一种类似于CD5缺失时发生的方式促进细胞的阳性选择。与此一致的是，即使在没有转基因TCR的情况下，缺乏CD2和CD5的复合纯合子也显示出阳性选择增强的证据。尽管观察到阳性选择增强，但当转基因胸腺细胞和成熟T淋巴细胞用适当抗原刺激时，CD2的缺乏与增殖反应和干扰素-γ产生的缺陷有关。这些发现提出了一种可能性，即胸腺中对选择配体的敏感性受损可能提供一种选择优势，从而提高某些TCR阳性选择的效率。此外，结果突出了CD2在胸腺细胞选择和T细胞免疫反应中发挥不同作用的潜力。
