Inhibitory effects of anti-interleukin 2 receptor and anti-L3T4 antibodies on delayed type hypersensitivity: the role of complement and epitope.
Although it is often assumed that anti-T cell antibodies mediate immunosuppression by targeting T cells for destruction, other activities should be considered. To dissect the mechanisms by which anti-L3T4 and anti-interleukin 2 receptor (IL 2R) monoclonal antibodies (Mab) mediate immunosuppression, the effects of anti-L3T4 and two complement-fixing anti-IL 2R Mab of the same isotype, but defining functionally distinct epitopes, were probed in a delayed type hypersensitive (DTH) model using BALB/c as well as two C5-deficient mouse strains. Low doses of anti-L3T4 and the M7/20 anti-IL 2R Mab, which competitively blocks IL 2 binding, inhibit DTH in BALB/c mice whereas an anti-receptor antibody which does not block the IL 2 binding site did not effectively abrogate DTH. Interestingly, anti-L3T4, but not M7/20 anti-IL 2 Mab treatment blocked DTH in the C5-deficient strains. On the other hand, M7/20 does not cause immunosuppression solely by blocking the IL 2R from occupancy by IL 2 because binding to T blasts by M7/20 is equivalent in BALB/c and C5-deficient strains. Consequently, immunosuppression mediated by anti-IL 2R Mab is dependent on both IL 2 receptor site blockade and C5. Clearly, anti-L3T4 and M7/20 have disparate requirements for C5 in mediating immunosuppression. There can be no doubt that factors other than the cellular targeting patterns influence the immunosuppressive activities of Mab. Ideally, anti-T cell Mab should fix complement and inhibit T cell function.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D003182:Complement C5 / Q000172:deficiency; D003165:Complement System Proteins / Q000502:physiology*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D011971:Receptors, Immunologic / Q000276:immunology*; D015375:Receptors, Interleukin-2; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D003182:Complement C5; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D003165:Complement System Proteins