Roberts K, Yokoyama W M, Kehn P J, Shevach E M
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1991 Jan 1;173(1):231-40. doi: 10.1084/jem.173.1.231.
Constitutive production of cytokines was observed in 3 of 12 gamma/delta T cell lines derived from murine epidermis and correlated with the expression of the C gamma 4, V delta 6 T cell receptor (TCR). After adaptation of one of the lines (T195/BW) to serum-free culture conditions, cessation of the "spontaneous" production of interleukin 4 (IL-4) was observed and IL-4 production could then by induced by the addition of RGD-containing extracellular matrix (ECM) proteins to the culture. The response to the ECM proteins could be completely inhibited by a mAb to the murine vitronectin receptor (VNR). However, the induction of IL-4 production could also be inhibited by anti-CD3 and by an anti-clonotypic mAb to the TCR-gamma/delta of T195/BW. As TCR-gamma/delta loss mutants of T195/BW also failed to respond to ECM proteins, these data demonstrate that engagement of the VNR by its ligand is necessary, but not sufficient, for the induction of IL-4 production. Furthermore, the VNR is expressed by many other T cell clones (both gamma/delta and alpha/beta), none of which produce lymphokines constitutively. Taken together, these observations strongly favor the view that not only is coexpression of the VNR and TCR required for the induction of IL-4 production, but that the TCR must also be engaged by its ligand, most likely a cell surface antigen expressed by the hybridoma itself.
在源自小鼠表皮的12个γ/δ T细胞系中的3个中观察到细胞因子的组成型产生，且这与Cγ4、Vδ6 T细胞受体（TCR）的表达相关。在其中一个细胞系（T195/BW）适应无血清培养条件后，观察到白细胞介素4（IL-4）“自发”产生停止，然后通过向培养物中添加含RGD的细胞外基质（ECM）蛋白可诱导IL-4产生。对ECM蛋白的反应可被抗小鼠玻连蛋白受体（VNR）的单克隆抗体完全抑制。然而，IL-4产生的诱导也可被抗CD3以及抗T195/BW的TCR-γ/δ的抗克隆型单克隆抗体抑制。由于T195/BW的TCR-γ/δ缺失突变体也未能对ECM蛋白作出反应，这些数据表明其配体与VNR的结合对于IL-4产生的诱导是必要的，但不是充分的。此外，许多其他T细胞克隆（γ/δ和α/β）均表达VNR，但它们均不组成型产生淋巴因子。综上所述，这些观察结果强烈支持这样一种观点，即诱导IL-4产生不仅需要VNR和TCR的共表达，而且TCR还必须被其配体（很可能是杂交瘤自身表达的一种细胞表面抗原）结合。
