Locally administered monoclonal antibodies to lymphocyte function-associated antigen 1 and to L3T4 prevent cutaneous graft-vs-host disease.
In vivo treatment with mAb directed against T cell surface molecules has been shown to prevent or reverse graft-vs-host disease (GVHD) and experimental autoimmune diseases, where T cells play a critical role. In this study we investigated the effects of in vivo administration of anti-I-A, anti-L3T4, and anti-lymphocyte function-associated Ag 1 (LFA-1) mAb on the development of murine cutaneous GVHD and delayed-type hypersensitivity responses evoked by local transfer of class II-MHC Ag-restricted, cloned autoreactive T cells. Prevention of cutaneous GVHD was achieved with local administration of either anti-L3T4 or anti-LFA-1 mAb, but not with anti-I-A mAb, while delayed-type hypersensitivity responses were inhibited by all the mAb. These results indicate that an I-A Ag-independent mechanism may be also operative in the development of the cutaneous GVHD, unlike the delayed-type hypersensitivity responses. Anti-LFA-1 mAb appeared to be more potent at inhibiting cutaneous GVHD rather than delayed-type hypersensitivity responses, whereas anti-L3T4 mAb inhibited equally both the responses. These results suggest that LFA-1 molecule may be involved in the epidermal invasion of T cells. Treatment with anti-LFA-1 mAb was found to be still, although less, effective at preventing cutaneous GVHD, even if the mAb was administered after the development of cutaneous GVHD.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000943:Antigens, Differentiation / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control*; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000517:prevention & control; D007271:Injections, Intradermal; D007700:Kinetics; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D008810:Mice, Inbred C57BL; D012871:Skin Diseases / Q000473:pathology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000637:transplantation
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D016169:Lymphocyte Function-Associated Antigen-1