Parallel costimulatory pathways promote myelin basic protein-stimulated proliferation of encephalitogenic rat T cells.
Activation pathways responsible for myelin basic protein (MBP)-stimulated proliferation of encephalitogenic T cells were studied by derivation of new monoclonal antibodies against rat T cell surface proteins. These monoclonal antibodies were derived by immunization of Balb/c mice with THYB-2 T cell hybrids or with the GP2.E5 line of encephalitogenic T-helper cells. The LRTC1 mAb inhibited MBP-stimulated IL-2 production by THYB-2 hybrids but not by THYB-1 hybrids and did not inhibit the alternative response of MBP-induced growth inhibition by either hybrid subset. Although LRTC1 labeled virtually all rat leukocytes, it selectively inhibited proliferative responses to T cell mitogens but not to B cell mitogens. LRTC1 inhibited MBP-stimulated IL-2 production by GP2.E5 T cells but did not effectively block MBP-stimulated proliferation. Rather, LRTC1 acted in synergy with a second mAb (LRTC2) to effectively inhibit MBP-stimulated proliferation by GP2.E5 T cells. The observation that LRTC1 did not exhibit synergy with a third biologically active mAb (LRTC3) supported the hypothesis that LRTC1 and LRTC2 represented a specific combination of synergistic mAb. In contrast to the inhibitory activity on GP2.E5 T cells, LRTC1 and LRTC2 synergistically stimulated antigen-independent IL-2 production by the THYB-1 hybrid LSS-A1. These results support the hypothesis that GP2.E5 T cells respond to parallel costimulatory pathways that are respectively inhibited by LRTC1 and LRTC2 mAb. Furthermore, these synergistic mAb exhibited inhibitory or stimulatory activities that may be diagnostic of distinct T-helper cell subsets. These novel mAb may thereby facilitate studies of costimulatory pathways and T-helper cell subsets in the pathogenesis of autoimmune disease.
Mannie
M D
MD
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354.
Morrison-Plummer
J
J
Torres-Garcia
B
B
Hannaway
C
C
Jones
C
C
Smith
A M
AM
D000818:Animals; D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D001402:B-Lymphocytes / Q000276:immunology; D001667:Binding, Competitive; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006822:Hybrid Cells / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007376:Interleukin-2; D004676:Myelin Basic Protein