Ceuppens J L, Baroja M L
J Immunol. 1986 Sep 15;137(6):1816-21.
Activation of human peripheral blood T cells by the anti-CD3 antibody OKT3 has been shown to require not only cross-linking of CD3 molecules with multimeric binding of the Fc part of OKT3 to a solid support, but also a second accessory cell-provided signal. Accordingly, measurement of T cell activation in cultures of highly enriched T cells with solid-phase-bound OKT3 can be used to investigate whether other agents can replace accessory cells. In this study we examined the capacity of anti-CD5 monoclonal antibodies to provide the additional activation signal. Resting T cells were prepared by isolating E rosette-positive cells, by removing OKM1(+) and HLA-DR(+) cells by panning, and by subsequent treatment of the cells with L-leucine methyl ester to kill remaining monocytes. These T cells were unresponsive to phytohemagglutinin (PHA) or to solid-phase-bound OKT3. However, when cultured in the presence of an anti-CD5 monoclonal antibody (anti-Leu-1, OKT1, or anti-T1), a proliferative response to solid-phase-bound OKT3 (but not to soluble OKT3 or to PHA) was observed. Anti-CD5 had no functional effect by itself, but in association with solid-phase-bound OKT3 it enhanced IL 2 receptor expression and IL 2 production and it initiated T cell proliferation. T cell proliferation under these conditions could be inhibited by an IL 2 receptor blocking antibody anti-Tac, thus confirming that anti-CD5 provides the second signal for an IL 2-dependent pathway of T cell proliferation. Preincubation of T cells with anti-Leu-1 or OKT1 resulted in complete loss of CD5 antigenicity, and such CD5 modulation was sufficient to induce a proliferative response to solid-phase-bound OKT3. It is concluded that in T cell activation by solid-phase-bound OKT3 the necessary additional signal can be provided by modulation of the CD5 antigen with an anti-CD5 antibody. CD5 therefore appears to be a positive signal receptor on the T cell membrane, whose physiologic ligand still has to be determined.
抗CD3抗体OKT3激活人外周血T细胞已表明不仅需要CD3分子通过OKT3的Fc部分与固相支持物的多聚体结合进行交联，还需要第二个辅助细胞提供的信号。因此，在高纯度T细胞与固相结合的OKT3培养物中测量T细胞激活可用于研究其他试剂是否能替代辅助细胞。在本研究中，我们检测了抗CD5单克隆抗体提供额外激活信号的能力。通过分离E花环阳性细胞、通过淘选去除OKM1(+)和HLA-DR(+)细胞以及随后用L-亮氨酸甲酯处理细胞以杀死剩余单核细胞来制备静息T细胞。这些T细胞对植物血凝素（PHA）或固相结合的OKT3无反应。然而，当在抗CD5单克隆抗体（抗Leu-1、OKT1或抗T1）存在下培养时，观察到对固相结合的OKT3（但对可溶性OKT3或PHA无反应）的增殖反应。抗CD5本身无功能作用，但与固相结合的OKT3联合时可增强IL-2受体表达和IL-2产生，并启动T细胞增殖。在这些条件下的T细胞增殖可被IL-2受体阻断抗体抗Tac抑制，从而证实抗CD5为T细胞增殖的IL-2依赖性途径提供第二个信号。用抗Leu-1或OKT1预孵育T细胞导致CD5抗原性完全丧失，且这种CD5调节足以诱导对固相结合的OKT3的增殖反应。得出结论，在固相结合的OKT3激活T细胞过程中，必要的额外信号可通过用抗CD5抗体调节CD5抗原提供。因此，CD5似乎是T细胞膜上的一种阳性信号受体，其生理配体仍有待确定。
