Two-step activation of T cells, clonal expansion and subsequent Th1 cytokine production, is essential for the development of clinical autoimmune encephalomyelitis.
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.
Jee
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Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
Matsumoto
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Y
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
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