Nieto M A, González A, López-Rivas A, Diaz-Espada F, Gambón F
Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.
J Immunol. 1990 Sep 1;145(5):1364-8.
In recent years, several studies have confirmed the clonal elimination of thymocytes with receptors that recognize Ag and MHC molecules present on the membrane of thymic stromal cells, a process that may be relevant to the establishment of self-tolerance. In our work, we show that anti-CD3 treatment of single positive CD4+ or CD8+ human medullary thymocytes (obtained by anti-CD1a plus C) induces their apoptotic death. Some events commonly associated with the early steps of normal activation (IL-2R expression, increase in cytoplasmic Ca2+) are also induced after anti-CD3 treatment. Nevertheless, IL-2 is not secreted by these activated cells. The addition of exogenous IL-2 inhibits the apoptosis induced by anti-CD3. We suggest that the lack of secretion of IL-2 by medullary thymocytes may be a physiologic mechanism implicated in the process of negative selection that leads to tolerance.
近年来，多项研究证实，胸腺细胞会通过其受体对胸腺基质细胞膜上存在的抗原和主要组织相容性复合体（MHC）分子进行识别，从而发生克隆清除，这一过程可能与自身耐受性的建立有关。在我们的研究中，我们发现，用抗CD3处理单阳性CD4⁺或CD8⁺人髓质胸腺细胞（通过抗CD1a加补体C获得）会诱导其凋亡死亡。抗CD3处理后，还会诱导一些通常与正常激活早期步骤相关的事件（白细胞介素-2受体表达、细胞质钙离子增加）。然而，这些活化细胞不会分泌白细胞介素-2。添加外源性白细胞介素-2可抑制抗CD3诱导的凋亡。我们认为，髓质胸腺细胞缺乏白细胞介素-2分泌可能是参与导致耐受性的阴性选择过程的一种生理机制。
