Bai Yalai, Fu Shuang, Honig Shaun, Wang Yinong, Qin Lihui, Chen Dan, Bromberg Jonathan S
Carl C. Icahn Institute For Gene Therapy and Molecular Medicine, and the Recanati/Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Am J Transplant. 2002 Aug;2(7):618-26. doi: 10.1034/j.1600-6143.2002.20706.x.
CD2 and 2B4 (CD244) are members of the immunoglobulin gene superfamily and are both ligands for another family member, CD48. CD2 is widely distributed on T, NK, and B cells and some antigen-presenting cells, while 2B4 is expressed on NK and some T cells and monocytes and is known to participate in NK cytotoxicity. Since indefinite allograft survival could be obtained by a combination of anti-CD48 plus anti-CD2 mAb administration, it was important to determine the role of 2B4 blockade in allograft rejection. MAbs directed against CD2, CD48, or 2B4 were administered singly or in pairs to cardiac allograft recipients. The experiments show that only anti-CD2 plus anti-CD48 mAbs result in indefinite allograft survival, while anti-CD2 plus anti-2B4 mAbs substantially prolong graft survival, and anti-CD48 plus anti-2B4 mAbs were no better than each mAb alone. The effect of these mAbs on anti-CD3 mAb and alloantigen-driven proliferation and IFN-gamma production were also assessed. In general, anti-CD2 inhibited both anti-CD3 mAb and alloantigen-driven responses, while anti-CD48 inhibited only anti-CD3 mAb but not alloantigen-driven proliferative and cytokine responses. Anti-2B4 mAbs were generally ineffective alone. Combinations of mAbs were more effective than single mAbs only in alloantigen-driven proliferation, commensurate with allograft survival results. Using CD2-/- and CD48-/- T cells and antigen-presenting cells, we also demonstrate that these inhibitory mAbs act primarily by blocking intercellular interactions, rather than directly delivering negative signals to T cells. These results suggest that, unlike CD2, 2B4 is not a potent regulatory molecule or ligand for CD48 in the response to alloantigen. Blocking the 2B4-CD48 receptor-ligand pair does not inhibit T-cell responses and alloreactivity to the same degree as CD2-CD48 blockade.
CD2和2B4（CD244）是免疫球蛋白基因超家族的成员，且二者都是另一个家族成员CD48的配体。CD2广泛分布于T细胞、自然杀伤（NK）细胞和B细胞以及一些抗原呈递细胞上，而2B4在NK细胞、一些T细胞和单核细胞上表达，并且已知其参与NK细胞的细胞毒性作用。由于联合给予抗CD48单克隆抗体（mAb）和抗CD2 mAb可实现同种异体移植物的无限期存活，因此确定阻断2B4在同种异体移植物排斥反应中的作用很重要。将针对CD2、CD48或2B4的单克隆抗体单独或成对给予心脏同种异体移植受体。实验表明，只有抗CD2加抗CD48单克隆抗体可导致同种异体移植物无限期存活，而抗CD2加抗2B4单克隆抗体可显著延长移植物存活时间，且抗CD48加抗2B4单克隆抗体并不比单独使用每种单克隆抗体效果更好。还评估了这些单克隆抗体对抗CD3单克隆抗体以及同种异体抗原驱动的增殖和γ干扰素（IFN-γ）产生的影响。一般来说，抗CD2抑制抗CD3单克隆抗体以及同种异体抗原驱动的反应，而抗CD48仅抑制抗CD3单克隆抗体，但不抑制同种异体抗原驱动的增殖和细胞因子反应。单独使用抗2B4单克隆抗体通常无效。单克隆抗体组合仅在同种异体抗原驱动的增殖方面比单一单克隆抗体更有效，这与同种异体移植物存活结果一致。利用CD2基因敲除（CD2-/-）和CD48基因敲除（CD48-/-）的T细胞和抗原呈递细胞，我们还证明这些抑制性单克隆抗体主要通过阻断细胞间相互作用发挥作用，而不是直接向T细胞传递负性信号。这些结果表明，与CD2不同，在同种异体抗原反应中，2B4不是一种有效的调节分子或CD48的配体。阻断2B4 - CD48受体 - 配体对并不像阻断CD2 - CD48那样同等程度地抑制T细胞反应和同种异体反应性。
