Subset-specific co-stimulatory signals are required for IL-2 production but not growth inhibition responses by T cell hybrids specific for myelin basic protein.
Two distinct types of T cell hybridomas (designated THYB-1 and T-HYB-2) were derived by fusing BW5147 thymoma cells with encephalitogenic T helper cells from Lewis rats. Both subsets required MHC-restricted presentation of determinants within the 72-86 peptide sequence of myelin basic protein (MBP) as a requisite signal for IL-2 production. Unlike THYB-1 hybrids, however, THYB-2 hybrids required additional accessory cell activities that were mediated by radiosensitive nonadherent (RS-NAdh) splenocytes (SPL). In this study, we describe two observations indicating that RS-NAdh SPL enable MBP-specific responses of THYB-2 hybrids by providing subset-specific co-stimulatory signals that act independently of antigen recognition pathways. First, RS-NAdh SPL were required by THYB-2 hybrids for MBP-stimulated IL-2 production but were not needed when MBP-specific inhibition of hybrid growth was used as an alternative measure of cellular activation. Second, PMA and ionomycin induced optimal IL-2 production by both THYB-1 hybrids and BW5147 thymoma cells but only stimulated low or marginal levels of IL-2 production by THYB-2 hybrids. Together, these observations indicate that RS-NAdh SPL were required for the specific response of IL-2 production regardless of whether the response was stimulated by antigen or by mitogens that bypass initial antigen recognition events. This study thereby provides additional evidence that distinct stimulus-response relationships define two T-helper cell lineages in experimental autoimmune encephalomyelitis.
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109-0620.
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D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D006825:Hybridomas / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013945:Thymoma / Q000276:immunology
D007375:Interleukin-1; D007376:Interleukin-2; D008934:Mitogens; D004676:Myelin Basic Protein