EFFICACY OF ANTI-INTERCELLULAR ADHESION MOLECULE-1 IMMUNOTHERAPY ON IMMUNE-RESPONSES TO ALLOGENEIC HEPATOCYTES IN MICE

Adhesion molecules appear to play important roles in vascularized orga n allograft rejection, because antibodies directed against them are ef fective in prolonging survival of vascularized organ allografts in rod ents. However, the efficacy of these agents for cellular allografts is unknown, The current studies were undertaken to determine the role of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on host immune responses to purified hepatocytes. Host mice (C3H, H-2(k)) grafted with hepatocytes in sponge matrix all ografts (HC-SMA) received IgG isotype control, anti-ICAM-1, or anti-VC AM-1 monoclonal antibody (mAb) on days 0 through 9 after grafting. Twe lve to 14 days later, host cells infiltrating the HC-SMA were assessed for the development of allospecific cytolytic T cells (allo-CTLs). Tr eatment with anti-ICAM-1 or anti-VCAM-1 mAb resulted in significantly decreased recruitment of host cells into HC-SMA (P < .035). However, o nly anti-ICAM-1 mAb resulted in abrogation of development of allo-CTLs in HC-SMA (P = .001), C3H (H-2(k)) hosts grafted with allogeneic hepa tocytes from control C57BL/6 (H-2(b)) or ICAM-1 knockout [H-2(b)] mice elicited the development of allo-CTLs in HC-SMA (P = not significant) . Furthermore, there was no difference in the development of allo-CTLs in HC-SMA of control hosts [C57BL/6, H-2(b)] compared with ICAM-1 kno ckout hosts (H-2(b)) (P = not significant). Treatment with anti-ICAM-1 mAb had no effect on the development of allo-CTLs in ICAM-1 knockout (H-2(b)) hosts bearing HC-SMA. The immunosuppressive effect of host tr eatment with anti-ICAM-1 mAb does not appear to be a consequence of si mple blockage of donor hepatocyte or host immune cell expression of IC AM-1, but suggests a potential inhibitory effect on host immune cell a ctivation or function, as well as an effect on recruitment of host cel ls to the allograft.