McCabe S M, Riddle L, Nakamura G R, Prashad H, Mehta A, Berman P W, Jardieu P
Department of Immunology, Genentech, Inc., South San Francisco, California 94080-4990.
Cell Immunol. 1993 Sep;150(2):364-75. doi: 10.1006/cimm.1993.1204.
The leucocyte adhesion molecules lymphocyte functional antigen-1 (LFA-1; CD11a/CD18) and intercellular adhesion molecule-1 (ICAM-1; CD54) facilitate the cell-to-cell interactions which are required for the initiation of immune responses. The role of this interaction in the response to alloantigen was assessed by comparing the effects of monoclonal antibodies against these molecules to the effects of a soluble form of the ICAM-1 molecule in the mixed lymphocyte response (MLR). In contrast to the well-documented inhibitory effects of anti-ICAM-1 or anti-LFA-1 antibodies on mixed lymphocyte responses, we were unable to block these responses with the soluble form of ICAM-1 (sICAM-1). In contrast, the addition of sICAM-1 to these cultures resulted in a two- to sixfold enhancement in the T-cell proliferative response to alloantigen over the normal response. Unlike previous reports, the biological activity of sICAM-1 was not dependent on generation of a solid-phase form of the molecule. The enhanced proliferative response correlated with an increase in the level of TNF-alpha detected in the MLR supernatants and could be blocked by antibodies to TNF-alpha. sICAM-1 had no effect on proliferation or cytokine production in the absence of alloantigen. These results suggest that antibodies which block ICAM-1/LFA-1 not only block the adhesion which is required to stabilize cell-to-cell contact, but also block the costimulatory signal which is required for T-cell activation.
白细胞黏附分子淋巴细胞功能相关抗原-1（LFA-1；CD11a/CD18）和细胞间黏附分子-1（ICAM-1；CD54）促进了免疫反应启动所需的细胞间相互作用。通过比较针对这些分子的单克隆抗体与可溶性ICAM-1分子形式在混合淋巴细胞反应（MLR）中的作用，评估了这种相互作用在同种异体抗原反应中的作用。与抗ICAM-1或抗LFA-1抗体对混合淋巴细胞反应的明确抑制作用相反，我们无法用可溶性ICAM-1（sICAM-1）阻断这些反应。相反，向这些培养物中添加sICAM-1导致T细胞对同种异体抗原的增殖反应比正常反应增强了2至6倍。与先前的报道不同，sICAM-1的生物学活性不依赖于该分子固相形式的产生。增殖反应增强与MLR上清液中检测到的TNF-α水平升高相关，并且可以被抗TNF-α抗体阻断。在没有同种异体抗原的情况下，sICAM-1对增殖或细胞因子产生没有影响。这些结果表明，阻断ICAM-1/LFA-1的抗体不仅阻断了稳定细胞间接触所需的黏附，还阻断了T细胞激活所需的共刺激信号。
