Treatment of murine lupus with monoclonal antibodies to lymphocyte function-associated antigen-1: dose-dependent inhibition of autoantibody production and blockade of the immune response to therapy.
Monoclonal antibodies (mAb) to lymphocyte function-associated antigen-1 (LFA-1) have been used successfully in vivo to inhibit immune responses and to block inflammatory reactions. To determine whether these effects of anti-LFA-1 could retard autoimmune disease, we treated lupus-prone NZB/NZW F1 (B/W) mice with a rat mAb to LFA-1 (anti-CD11a). Mice received high-dose therapy (500 micrograms twice weekly), low-dose therapy (40 micrograms thrice weekly), or phosphate-buffered saline from age 5 months to age 10 months. Treatment with high doses of anti-CD11a suppressed both the immune response to the rat mAb and the production of autoantibodies to double-stranded DNA. In contrast, treatment with low doses of anti-CD11a elicited an immune response to the rat mAb and did not suppress autoantibody production. The immunosuppressive effects of high doses of anti-CD11a were not due to target cell depletion. In fact, treatment induced a marked lymphocytosis which involved all lymphocyte subsets equally. Despite inhibiting autoantibody production, high-dose therapy had only modest effects on longevity.
Connolly
M K
MK
Arthritis/Immunology Section, Veterans Administration Medical Center, San Francisco, California 94121.
Kitchens
E A
EA
Chan
B
B
Jardieu
P
P
Wofsy
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007167:Immunotherapy; D008177:Lupus Vulgaris / Q000276:immunology* / Q000628:therapy*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology* / Q000494:pharmacology / Q000502:physiology; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008218:Lymphocytosis / Q000139:chemically induced / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D016169:Lymphocyte Function-Associated Antigen-1; D004247:DNA