title: T-bet is essential for the progression of experimental autoimmune encephalomyelitis.
abstract: Experimental autoimmune encephalomyelitis (EAE) is mediated by myelin-specific CD4+ T helper 1 (Th1) cells, while recovery from the disease is associated with the presence of Th2 cells. Here we used animals with targeted deletion of the T-bet gene to determine its role in the progression of EAE. T-bet regulates the production of interferon-gamma (IFN-gamma) in CD4+ and natural killer cells, and CD4+ T cells from T-bet-deficient mice were unable to differentiate into a Th1 phenotype. Moreover BALB/c mice deficient in T-bet were resistant to the induction of EAE disease, with minimal inflammatory infiltrates in the central nervous system. These mice were resistant to EAE induction even when PLP(180-199) peptide specific effector T cells from BALB/c wild type were transferred to BALB/c T-bet-deficient mice. This resistance to EAE is may be caused by the production of the anti-inflammatory cytokine interleukin-10 (IL-10) from the spleen cells upon ex vivo stimulation with PLP(180-199) peptide and in vivo presence in the central nervous system. There was no difference in the recall responses in spleen cells from T-bet-deficient and wild type mice; however, less secretion of IFN-gamma was observed from primed splenocytes. The expression of IFN-gamma was less in the central nervous system of T-bet-deficient mice whereas IL-10 was significantly higher in T-bet-deficient as compared to wild type mice. These data indicate that T-bet genes play a critical role in maintaining the encephalitogenic nature of CD4+ T cells in autoimmune responses during EAE disease progression.
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Narender
authors.initials: N
authors.lastname: Nath
authors.forename: Ratna
authors.initials: R
authors.lastname: Prasad
authors.forename: Shailendra
authors.initials: S
authors.lastname: Giri
authors.forename: Avtar K
authors.initials: AK
authors.lastname: Singh
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013116:Spinal Cord / Q000276:immunology; D013154:Spleen / Q000276:immunology; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors