Lin J, Yon R W, Chavin K D, Qin L, Woodward J, Ding Y, Yagita H, Bromberg J S
Department of Microbiology, Medical University of South Carolina, Charleston 29425, USA.
Transplantation. 1995 Apr 27;59(8):1162-71.
Anti-CD2 mAbs suppress T cell immunity and prolong allograft survival in vivo while inducing the down-modulation of CD2 expression. Manipulation of cell surface molecules may be important in inducing tolerance, so down-modulation of CD2 expression on T cells by anti-CD2 mAbs was further defined with an in vitro model. The anti-CD2 mAb 12-15 caused CD2 expression on purified splenic T cells to decrease from 83.4 to 22.7% total positive cells while CD3, CD4, and CD8 expression remained unchanged. The expression of other adhesion molecules, LFA-1 alpha (CD11a), LFA-1 beta (CD18), Pgp-1 (CD44), CD45, MEL-14 (L-selectin), and VLA-4 alpha (CD49d), were all increased as a result of anti-CD2 treatment, whereas CD25 (IL-2R), CD48 (CD2 ligand), and ICAM-1 (CD54) remained unchanged. Kinetics showed that CD2 down-modulation was persistent and at the same magnitude from day 1 through day 7 of culture. Anti-CD2 mAb could down modulate CD2 on both CD4 and CD8 splenic lymphocyte subsets, thymocytes, and the T cell lymphoma EL-4; and, non-T cells did not seem to participate in the process of modulation. Mechanistic studies of mAb action showed that, in addition to 12-15, other anti-CD2 mAbs could cause down-modulation of T cell CD2 expression in an epitope and isotype dependent fashion and that CD2 down-modulation correlated with inhibition of receptor-driven T cell stimulation. Intact antibody, including the Fc portion, was required to induce CD2 down-modulation, and additional experiments suggested an interaction with an Fc gamma R other than Fc gamma RII or Fc gamma RIII. CD2 down-modulation did not change with the addition of the cytokines IL-1, IL-2, IL-6, IL-10, TNF alpha, or TGF-beta 1. These results show that anti-CD2 mAbs significantly and persistently down-modulate CD2 on various T cell subpopulations. The mAbs must interact with both the CD2 receptor and an Fc gamma R. CD2 down-modulation is accompanied by changes in the array of other T cell surface receptors that may contribute to mechanisms of anti-CD2-induced immunosuppression.
抗CD2单克隆抗体在体内可抑制T细胞免疫并延长同种异体移植物存活时间，同时诱导CD2表达下调。细胞表面分子的调控在诱导免疫耐受中可能很重要，因此利用体外模型进一步明确了抗CD2单克隆抗体对T细胞上CD2表达的下调作用。抗CD2单克隆抗体12 - 15可使纯化脾T细胞上的CD2表达从总阳性细胞的83.4%降至22.7%，而CD3、CD4和CD8表达保持不变。抗CD2处理后，其他黏附分子LFA - 1α（CD11a）、LFA - 1β（CD18）、Pgp - 1（CD44）、CD45、MEL - 14（L - 选择素）和VLA - 4α（CD49d）的表达均增加，而CD25（IL - 2R）、CD48（CD2配体）和ICAM - 1（CD54）保持不变。动力学研究表明，从培养第1天到第7天，CD2下调持续存在且幅度相同。抗CD2单克隆抗体可下调CD4和CD8脾淋巴细胞亚群、胸腺细胞以及T细胞淋巴瘤EL - 4上的CD2；并且，非T细胞似乎不参与这种调控过程。单克隆抗体作用的机制研究表明，除了12 - 15外，其他抗CD2单克隆抗体可通过表位和同种型依赖性方式导致T细胞CD2表达下调，且CD2下调与受体驱动的T细胞刺激抑制相关。诱导CD2下调需要完整的抗体，包括Fc部分，进一步实验表明其与FcγRII或FcγRIII以外的FcγR相互作用。添加细胞因子IL - 1、IL - 2、IL - 6、IL - 10、TNFα或TGF - β1后，CD2下调无变化。这些结果表明，抗CD2单克隆抗体可显著且持续地下调各种T细胞亚群上的CD2。单克隆抗体必须与CD2受体和FcγR相互作用。CD2下调伴随着其他T细胞表面受体阵列的变化，这可能有助于抗CD2诱导的免疫抑制机制。
