Genetic control of the development of experimental allergic encephalomyelitis in rats. Separation of MHC and non-MHC gene effects.
Experimental allergic encephalomyelitis (EAE)-susceptible Lew and EAE-resistant Brown Norway (BN) rats and the corresponding MHC congenic strains were examined for their ability to develop clinical and histologic EAE. The ability of T cells from these animals to proliferate in vitro in response to whole guinea pig (GP) myelin basic protein (MBP), rat MBP, and to the major encephalitogenic peptide of GP MBP 66-88 (GP 68-88) was also assessed. We found that Lewis (Lew) was highly susceptible and showed good T cell responses to GP, MBP, rat MBP, and GP 68-88. Lew.1N (BN MHC on Lew background) and BN were not susceptible and T cells from these strains showed significant responses to GP MBP, but not to rat MBP or GP 68-88. Although BN.B1 (Lew MHC on BN background) was not susceptible to actively induced EAE, MBP-specific Lew T cells could transfer severe disease to BN.B1. BN.B1 T cells showed responses to GP-MBP, rat MBP, and GP 68-88 and, when transferred to naive BN.B1 or Lew, induced only mild clinical EAE in both strains. Increasing the number of T cells from BN.B1 had no effect on the severity of clinical symptoms in either recipient, suggesting some deficiency in the T cell repertoire that is necessary for induction of severe EAE. These results suggest that 1) the T cell response to rat MBP and GP68-88 (but not to sites other than 68-88 in GP MBP) is necessary for susceptibility to EAE; 2) the ability to respond to both rat MBP and GP 68-88 is determined by the MHC gene products on APC; and 3) given a permissive MHC, the T cell response that results in EAE is influenced by non-MHC genes.
Happ
M P
MP
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Wettstein
P
P
Dietzschold
B
B
Heber-Katz
E
E
D000818:Animals; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006168:Guinea Pigs; D006649:Histocompatibility Antigens / Q000235:genetics*; D007116:Immunization, Passive; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation
D000939:Epitopes; D006649:Histocompatibility Antigens; D004676:Myelin Basic Protein; C038353:histocompatibility antigens RT, rat