Relative susceptibility of SJL/J and B10.S mice to experimental allergic encephalomyelitis is correlated with high and low responsiveness to myelin basic protein.
SJL/J mice are highly susceptible to actively induced experimental allergic encephalomyelitis (EAE), whereas B10.S mice are not. Yet both strains share the H-2s major histocompatibility complex (MHC) haplotype. In order to help determine the cellular basis for the disparate susceptibility to EAE, the antigen-specific in vitro proliferative responses of lymph node (LN) T cells from SJL/J and B10.S mice primed with porcine myelin basic protein (MBP) were assessed. The results indicated that SJL/J mice were high responders and B10.S mice were low responders to both porcine and murine MBP, as demonstrated by limiting dilution analyses and cloning efficiency analysis of MBP-reactive T cells. The low response of B10.S mice to MBP was not due to elevated suppressor cell activity or to a discernible defect in antigen-presenting cell activity. Rather, it appeared to be due to a paucity (or defect in function) of high affinity MBP-reactive T cells in B10.S as compared to SJL/J mice. This difference in MBP responsiveness must, by necessity, be linked to non-MHC background genes. Therefore, assuming that the relative number of MBP-reactive T cells parallels that of EAE-effector T cells in SJL/J and B10.S mice (as separate in vivo studies indicate), the present results suggest that differences in the T cell repertoire for the encephalitogenic determinants of MBP may contribute significantly to the observed differences in antigen reactivity, and may relate to differences in susceptibility to EAE.
Binder
T A
TA
Department of Pathology, University of Connecticut Health Center, Farmington 06030.
Clark
R B
RB
Goldschneider
I
I
D000818:Animals; D002455:Cell Division; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology*; D000939:Epitopes; D005260:Female; D020022:Genetic Predisposition to Disease; D007201:Indicator Dilution Techniques; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008818:Mice, Neurologic Mutants / Q000502:physiology*; D004676:Myelin Basic Protein / Q000276:immunology / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D000939:Epitopes; D004676:Myelin Basic Protein