title: Emergence of a radioresistant population of co-stimulatory splenocytes during remission of experimental autoimmune encephalomyelitis in Lewis rats.
abstract: T-cell hybridomas specific for myelin basic protein (MBP) were used to assess regulation of co-stimulatory signals during remission of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Both THYB-1 and THYB-2 subsets of T-cell hybridomas recognize class II major histocompatibility complex-restricted determinants in the 72-86 encephalitogenic region of MBP. However, THYB-2 hybrids uniquely express additional requirements for co-stimulatory signals from radiosensitive splenocytes (SPL) to support the response of MBP-stimulated IL-2 production. Hence, this subset provides a means to study regulation of THYB-2 specific co-stimulatory signals during the course of EAE. This study revealed that sensitization of Lewis rats with MBP in complete Freund's adjuvant induced a radioresistant subpopulation of co-stimulatory SPL that emerged during the remission phase of EAE. These radioresistant SPL provided specific accessory cell activities that fulfilled the co-stimulatory requirements of THYB-2 hybrids. These findings support the hypothesis that in vivo activation events elicit radioresistance in an emergent clonally expanding population of antigen-specific lymphocytes. A central prediction of this hypothesis is that cellular activation should confer radioresistance to co-stimulatory lymphocytes. This prediction was verified by the observation that in vitro activation of naive SPL with different B- and T-cell mitogens conferred radioresistance to co-stimulatory SPL. Mitogenic activation not only induced radioresistance but also dramatically augmented co-stimulatory activity of purified B cells. In summary, the results of this study support the hypothesis that in vivo activation of co-stimulatory lymphocytes may regulate activities of encephalitogenic T-helper cells during progression and remission of EAE.
authors.affiliation: Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858.
authors.forename: M D
authors.initials: MD
authors.lastname: Mannie
authors.forename: S L
authors.initials: SL
authors.lastname: Watkins
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006825:Hybridomas; D007114:Immunization; D007376:Interleukin-2 / Q000096:biosynthesis; D008214:Lymphocytes / Q000528:radiation effects*; D004676:Myelin Basic Protein / Q000276:immunology; D011836:Radiation Tolerance; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets
chemical_list: D007376:Interleukin-2; D004676:Myelin Basic Protein