Monoclonal antibody-induced inhibition of relapsing EAE in SJL/J mice correlates with inhibition of neuroantigen-specific cell-mediated immune responses.
Relapsing experimental allergic encephalomyelitis (R-EAE) in SJL/J mice was examined in relation to the development of neuroantigen-specific T cell proliferative (Tprlf) and delayed-type hypersensitivity (DTH) responses. R-EAE was induced by injecting syngeneic mouse spinal cord homogenate in CFA on days 0 and 7 over the shaved flanks of female SJL/J mice. Mice primed in this manner exhibited significant Tprlf and DTH responses specific for both major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP). A time course comparison between the induction of R-EAE and the development of neuroantigen-specific cell-mediated immune (CMI) responses (Tprlf and DTH) revealed that the MBP- and PLP-specific Tprlf and DTH responses peaked prior to the onset of initial clinical symptoms and the DTH responses remained at significant levels throughout the relapsing course of the disease. Monoclonal antibodies were used to determine whether in vivo inhibition of class II-restricted Tprlf and DTH responses correlated with inhibition of R-EAE. In vivo administration of a total of 100 micrograms anti-L3T4 antibody, but not anti-Lyt-2 antibody, resulted in delayed onset and reduced severity of clinical signs of R-EAE concomitant with significantly reduced levels of MBP- and PLP-specific Tprlf and DTH responses. Treatment with a total of 300 micrograms of purified anti-L3T4 resulted in total abrogation of R-EAE induction and neuroantigen-specific CMI. Thus, clinical signs of R-EAE were found to correlate with the activity of neuroantigen-specific, class II-restricted T cells.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology*; D011510:Proteolipids / Q000276:immunology*; D051381:Rats; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D004676:Myelin Basic Protein; D011510:Proteolipids