Geppert T D, Nguyen H, Lipsky P E
Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Eur J Immunol. 1992 Jun;22(6):1379-83. doi: 10.1002/eji.1830220608.
Recent evidence has demonstrated that cross-linking class I major histocompatibility complex (MHC) molecules on human T cells with monoclonal antibodies (mAb) triggers T cell activation. The only known natural ligand for MHC class I molecules is CD8. Therefore, the possibility that CD8+ T cells might provide activation signals to other T cells by engaging MHC class I molecules was examined by culturing CD4+ peripheral blood T cells with Chinese hamster ovary cells (CHO) cells that had been transfected with the alpha chain or alpha and beta chains of CD8 and assessing interleukin (IL)-2 production. CD4+ T cells did not secrete IL-2 when cultured alone, with control or CD8+ CHO cells. In contrast, CD4+ T cells produced IL-2 when cultured with CD8+ CHO cells and co-stimulated with phorbol myristate acetate (PMA) or mAb to CD3 or CD28. PMA stimulated substantially less IL-2 when control CHO cells were employed and the mAb to CD3 and CD28 did not stimulate IL-2 production in the presence of control CHO cells. The co-stimulatory activity of CD8+ CHO cells was completely eliminated by mAb to CD8 or MHC class I molecules. The data demonstrate that CD8 can interact with MHC class I molecules expressed on T cells and deliver a costimulatory signal that increases IL-2 production. Thus, engagement of MHC class I molecules by its natural ligand, CD8, provides an activation signal to T cells. Under some circumstances, such interactions may amplify the responses of T cells.
最近的证据表明，用单克隆抗体（mAb）使人类T细胞上的I类主要组织相容性复合体（MHC）分子交联会触发T细胞活化。MHC I类分子唯一已知的天然配体是CD8。因此，通过将CD4 +外周血T细胞与已转染CD8α链或α和β链的中国仓鼠卵巢细胞（CHO）一起培养，并评估白细胞介素（IL）-2的产生，来研究CD8 + T细胞是否可能通过与MHC I类分子结合为其他T细胞提供活化信号。单独培养、与对照或CD8 + CHO细胞一起培养时，CD4 + T细胞不分泌IL-2。相反，当与CD8 + CHO细胞一起培养并用佛波酯肉豆蔻酸酯乙酸酯（PMA）或抗CD3或CD28的mAb共刺激时，CD4 + T细胞产生IL-2。当使用对照CHO细胞时，PMA刺激产生的IL-2要少得多，并且在存在对照CHO细胞的情况下，抗CD3和CD28的mAb不会刺激IL-2的产生。抗CD8或MHC I类分子的mAb完全消除了CD8 + CHO细胞的共刺激活性。数据表明，CD8可以与T细胞上表达的MHC I类分子相互作用，并传递增加IL-2产生的共刺激信号。因此，MHC I类分子与其天然配体CD8的结合为T细胞提供了活化信号。在某些情况下，这种相互作用可能会放大T细胞的反应。
