Antibodies against I-A and I-E determinants inhibit the activation and function of encephalitogenic T-lymphocyte lines.
Two monoclonal antibodies, OX-6 and OX-17, were used to evaluate respectively the roles of I-A and I-E major histocompatibility complex Class II gene products in the in vitro activation and subsequent function in recipient rats of encephalitogenic T-cell lines. Activation of the T-cell lines with guinea pig myelin basic protein (GP-BP) presented by accessory cells (APC) resulted in an increase in the number of blast cells in culture and was reflected by increased uptake of [3H]thymidine [( 3H]Tdy). The number of blasts recovered and [3H]Tdy uptake during activation was reduced drastically in the presence of OX-6, but to a much lesser extent in the presence of OX-17. OX-6 but not OX-17 appeared to block T-cell activation primarily by inhibiting APC function, since preincubation of APC but not T cells with OX-6 before stimulation resulted in complete inhibition of the cultures. After activation, the BP-1 T-cell line or D-9 clone transferred severe paralysis to normal recipient rats. Recipients of OX-6-treated BP-1 or D-9 T cells exhibited very mild or no signs, whereas recipients of OX-17-treated cells developed only slightly less severe experimental autoimmune encephalomyelitis (EAE) than recipients of untreated encephalitogenic control cultures. In contrast, treatment with OX-17 but not OX-6 reduced the ability of BP-reactive T cells to transfer delayed-type hypersensitivity reactions. Dermal testing with GP-BP in the ears of recipient rats just prior to onset of clinical signs decreased significantly the clinical intensity of EAE induced by activated BP-reactive T cells, but increased the clinical scores in rats which received unstimulated or OX-6-treated T cells. This potentiating effect of GP-BP was due most likely to the presentation of processed antigen to circulating BP-reactive T cells by APC in the ear. These results suggest that both the I-A and I-E gene products may contribute to the activation and subsequent function of encephalitogenic T cells, perhaps through separate mechanisms.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D004676:Myelin Basic Protein / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein