McCarthy S A, Kruisbeek A M, Uppenkamp I K, Sharrow S O, Singer A
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
Nature. 1988 Nov 3;336(6194):76-9. doi: 10.1038/336076a0.
The intrathymic differentiation process by which precursor cells derived from the bone marrow develop into immuno-competent T lymphocytes is poorly understood. Most thymocytes express both CD4 and CD8 accessory molecules, yet little is known about either the function of these molecules or the responsiveness of the CD4+8+ double positive thymocytes that bear them. Here, we address the possibility that CD4 engagement influences T-cell receptor (TCR) expression on developing thymocytes. We engaged CD4 molecules on murine thymocytes by in vivo injection of an anti-CD4 monoclonal antibody, which reduced the surface expression of CD4 on CD4+ thymocytes. More importantly, CD4 engagement also affected TCR expression on CD4+ thymocytes, but the effect on CD4+8+ double positive and CD4+8- single positive thymocytes was very different. CD4+8+ thymocytes responded to CD4 engagement by dramatically increasing surface expression of TCR, whereas CD4+8- thymocytes decreased surface expression of TCR. These results demonstrate that the effect of CD4 engagement on TCR expression is dependent upon the developmental state of the responding thymocyte, and, most interestingly, results in increased TCR expression by double positive thymocytes.
骨髓来源的前体细胞发育成为具有免疫活性的T淋巴细胞的胸腺内分化过程，目前仍了解甚少。大多数胸腺细胞同时表达CD4和CD8辅助分子，但对于这些分子的功能以及携带它们的CD4+8+双阳性胸腺细胞的反应性，人们却知之甚少。在此，我们探讨CD4参与是否会影响发育中的胸腺细胞上T细胞受体（TCR）的表达。我们通过体内注射抗CD4单克隆抗体使小鼠胸腺细胞上的CD4分子参与反应，这降低了CD4+胸腺细胞表面CD4的表达。更重要的是，CD4参与也影响了CD4+胸腺细胞上TCR的表达，但对CD4+8+双阳性和CD4+8-单阳性胸腺细胞的影响却大不相同。CD4+8+胸腺细胞对CD4参与的反应是显著增加TCR的表面表达，而CD4+8-胸腺细胞则降低TCR的表面表达。这些结果表明，CD4参与对TCR表达的影响取决于反应性胸腺细胞的发育状态，而且，最有趣的是，双阳性胸腺细胞的TCR表达会增加。
