title: Coronin 1-mediated naive T cell survival is essential for the development of autoimmune encephalomyelitis.
abstract: Autoimmune encephalomyelitis is a disease of the CNS that can develop when an initial peripheral inflammatory stimulus is followed by infiltration and reactivation of T lymphocytes in the CNS. We report a crucial role for coronin 1, which is essential for maintenance of the naive T cell pool, for the development of murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. In the absence of coronin 1, immunization with myelin oligoglycoprotein (MOG(35-55)) peptide largely failed to induce EAE symptoms, despite normal mobilization of leukocyte subsets in the blood, as well as effector cytokine expression comparable with wild-type T cells on polyclonal stimulation. Susceptibility of coronin 1-deficient mice to EAE induction was restored by transfer of wild-type CD4(+) T cells, suggesting that the observed resistance of coronin 1-deficient mice to EAE development is T cell intrinsic. Importantly, although coronin 1-deficient regulatory T cells (Tregs) showed a suppressor activity comparable with wild-type Tregs, Treg depletion failed to restore EAE development in coronin 1-deficient animals. These results suggest a hitherto unrecognized role of naive T cells in the development of autoimmune encephalomyelitis and reveal coronin 1 as a crucial modulator of EAE induction.
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Siegmund
authors.forename: Thomas
authors.initials: T
authors.lastname: Zeis
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kunz
authors.forename: Ton
authors.initials: T
authors.lastname: Rolink
authors.forename: Nicole
authors.initials: N
authors.lastname: Schaeren-Wiemers
authors.forename: Jean
authors.initials: J
authors.lastname: Pieters
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018984:Epitopes, T-Lymphocyte; D008840:Microfilament Proteins; D004676:Myelin Basic Protein; C072061:coronin proteins