High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice.
We have generated TCR transgenic mice (T/R+) specific for myelin basic protein (MBP) and crossed them to RAG-1-deficient mice to obtain mice (T/R-) that have T cells expressing the transgenic TCR but no other lymphocytes. Both T/R+ and T/R- mice carry, in the lymph nodes and spleen, large numbers of the potentially encephalitogenic CD4+ anti-MBP T cells. These cells respond to MBP in vitro but show no signs of activation in vivo. Nevertheless, approximately 14% of H-2u T/R+ and 100% of H-2u T/R- mice developed spontaneous experimental autoimmune encephalomyelitis (EAE) within 12 months. These data indicate that EAE can be mediated by CD4+ anti-MBP T cells in the absence of any other lymphocytes and that nontransgenic lymphocytes that are present in T/R+ but absent in T/R- mice have a protective effect. The data also suggest that spontaneous EAE may be triggered by an in situ activation of CD4+ anti-MBP cells in the nervous system.
Lafaille
J J
JJ
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Nagashima
K
K
Katsuki
M
M
Tonegawa
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology; D003433:Crosses, Genetic; D004679:Encephalomyelitis / Q000276:immunology*; D005434:Flow Cytometry; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D011506:Proteins / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D013154:Spleen / Q000276:immunology
D018398:Homeodomain Proteins; D004676:Myelin Basic Protein; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein