title: CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis.
abstract: The existence of T cells restricted for the MHC I-like molecule CD1 is well established, but the function of these cells is still obscure; one implication is that CD1-dependent T cells regulate autoimmunity. In this study, we investigate their role in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, using CD1-deficient mice on a C57BL/6 background. We show that CD1-/- mice develop a clinically more severe and chronic EAE compared with CD1+/+ C57BL/6 mice, which was histopathologically confirmed with increased demyelination and CNS infiltration in CD1-/- mice. Autoantigen rechallenge in vitro revealed similar T cell proliferation in CD+/+ and CD1-/- mice but an amplified cytokine response in CD1-/- mice as measured by both the Th1 cytokine IFN-gamma and the Th2 cytokine IL-4. Investigation of cytokine production at the site of inflammation showed a CNS influx of TGF-beta1-producing cells early in the disease in CD1+/+ mice, which was absent in the CD1-/- mice. Passive transfer of EAE using an autoreactive T cell line induced equivalent disease in both groups, which suggested additional requirements for activation of the CD1-dependent regulatory pathway(s). When immunized with CFA before T cell transfer, the CD1-/- mice again developed an augmented EAE compared with CD1+/+ mice. We suggest that CD1 exerts its function during CFA-mediated activation, regulating development of EAE both through enhancing TGF-beta1 production and through limiting autoreactive T cell activation, but not necessarily via effects on the Th1/Th2 balance.
authors.affiliation: Section for Medical Inflammation Research, Lund University, I11 Biomedicinskt Centrum, S-221 84 Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Teige
authors.forename: Ingrid
authors.initials: I
authors.lastname: Teige
authors.forename: Shahram
authors.initials: S
authors.lastname: Lavasani
authors.forename: Robert
authors.initials: R
authors.lastname: Bockermann
authors.forename: Emma
authors.initials: E
authors.lastname: Mondoc
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Shohreh
authors.initials: S
authors.lastname: Issazadeh-Navikas
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005838:Genotype; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D015994:Incidence; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D014611:Vaccination
chemical_list: D018949:Antigens, CD1; D016207:Cytokines; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C445081:myelin oligodendrocyte glycoprotein (35-55)