title: Two-step activation of T cells, clonal expansion and subsequent Th1 cytokine production, is essential for the development of clinical autoimmune encephalomyelitis.
abstract: Lewis rats immunized with guinea pig myelin basic protein (GPBP) emulsified with incomplete Freund's adjuvant (IFA) do not develop experimental autoimmune encephalomyelitis (EAE). However, we found that GPBP/IFA with pertussis toxin (PT) administration induced full-blown EAE. By comparing the immunological status of rats immunized with GPBP/IFA plus PT [PT (+) rats] with that of rats immunized with GPBP/IFA alone [PT (-) rats], we tried to elucidate the pathomechanisms of EAE. Analysis of the TCR clonality by CDR3 spectratyping revealed that Vbeta8.2 and Vbeta10 expansion of T cells occurred in both PT (-) and PT (+) rats, indicating that activation of T cells at this level is not sufficient for the development of clinical EAE. Quantitation of cytokine mRNA and protein revealed that PT (-) rats showed a Th2-dominant, while PT (+) rats showed a Th1-dominant, cytokine profile. Furthermore, administration of IL-12, but not of IFN-gamma and TNF-alpha, induced clinical EAE in GPBP/IFA-immunized animals. Taken together, two-step activation, activation of T cells bearing a particular type of TCR by antigen immunization and subsequent overproduction of Th1 cytokines, mainly IL-12 production, induced by appropriate adjuvants is essential for the development of clinical EAE.
authors.affiliation: Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Jee
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005620:Freund's Adjuvant / Q000276:immunology; D006168:Guinea Pigs; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology; D008055:Lipids; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D037342:Pertussis Toxin; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013116:Spinal Cord / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D010566:Virulence Factors, Bordetella
chemical_list: D016207:Cytokines; D008055:Lipids; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D010566:Virulence Factors, Bordetella; C114843:incomplete Freund's adjuvant; D018664:Interleukin-12; D005620:Freund's Adjuvant; D037342:Pertussis Toxin