Rothman B L, Kennure N, Kelley K A, Katz M, Aune T M
Institute of Arthritis and Autoimmunity, Miles Research Center, West Haven, CT 06516.
J Immunol. 1993 Dec 1;151(11):6036-42.
Regulation of lymphocyte responses to activation of the CD3/TCR complex by other cell surface proteins expressed on lymphocytes is a well established phenomenon. CD44 is an example of such a cell surface protein. Anti-CD44 mAb have been identified which either stimulate or inhibit lymphocyte function. Certain anti-CD44 mAb augment proliferation and IL-2 production by T cells stimulated through the CD2 or CD3/TCR pathways. An anti-CD44 mAb with opposing properties has also been identified. This mAb inhibits activation of human T cells by preventing the rise in [Ca2+]i stimulated by OKT3. The purpose of experiments reported here was to further characterize this phenomenon. The results show that the anti-CD44 mAb, 212.3, does not inhibit inositol phosphate turnover stimulated by OKT3 but does inhibit elevation of intracellular [Ca2+]i in these same cells. Addition of 212.3 to purified human T cells results in a rapid increase in intracellular levels of cAMP. Elevation of cAMP by 212.3 is time- and concentration-dependent. Activation of adenylate cyclase by forskolin also results in elevation of intracellular cAMP and inhibition of the increase in [Ca2+]i stimulated by OKT3. Taken together, these data suggest that CD44 may be positively coupled to adenylate cyclase and that activation of adenylate cyclase by the anti-CD44 mAb, 212.3, may mediate the inhibition of the OKT3-stimulated elevation of [Ca2+]i.
淋巴细胞上表达的其他细胞表面蛋白对CD3/TCR复合物激活所产生的淋巴细胞反应的调节是一个已被充分证实的现象。CD44就是这样一种细胞表面蛋白的例子。已经鉴定出了能刺激或抑制淋巴细胞功能的抗CD44单克隆抗体。某些抗CD44单克隆抗体可增强通过CD2或CD3/TCR途径刺激的T细胞的增殖和白细胞介素-2的产生。也鉴定出了一种具有相反特性的抗CD44单克隆抗体。这种单克隆抗体通过阻止OKT3刺激引起的细胞内钙离子浓度升高来抑制人T细胞的激活。本文报道的实验目的是进一步表征这一现象。结果表明，抗CD44单克隆抗体212.3并不抑制OKT3刺激引起的肌醇磷酸转换，但确实抑制了这些相同细胞内钙离子浓度的升高。将212.3添加到纯化的人T细胞中会导致细胞内cAMP水平迅速升高。212.3引起的cAMP升高具有时间和浓度依赖性。福斯可林激活腺苷酸环化酶也会导致细胞内cAMP升高，并抑制OKT3刺激引起的钙离子浓度升高。综上所述，这些数据表明CD44可能与腺苷酸环化酶呈正相关，并且抗CD44单克隆抗体212.3激活腺苷酸环化酶可能介导了对OKT3刺激引起的钙离子浓度升高的抑制作用。
