title: The neonatal CNS is not conducive for encephalitogenic Th1 T cells and B cells during experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) is thought to be a CD4+ T cell mediated autoimmune demyelinating disease of the central nervous system (CNS) that is rarely diagnosed during infancy. Cellular and molecular mechanisms that confer disease resistance in this age group are unknown. We tested the hypothesis that a differential composition of immune cells within the CNS modulates age-associated susceptibility to CNS autoimmune disease. C57BL/6 mice younger than eight weeks were resistant to experimental autoimmune encephalomyelitis (EAE) following active immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p) 35-55. Neonates also developed milder EAE after transfer of adult encephalitogenic T cells primed by adult or neonate antigen presenting cells (APC). There was a significant increase in CD45+ hematopoietic immune cells and CD45+ high side scatter granulocytes in the CNS of adults, but not in neonates. Within the CD45+ immune cell compartment of adults, the accumulation of CD4+ T cells, Gr-1+ and Gr-1- monocytes and CD11c+ dendritic cells (DC) was identified. A significantly greater percentage of CD19+ B cells in the adult CNS expressed MHC II than neonate CNS B cells. Only in the adult CNS could IFNγ transcripts be detected 10 days post immunization for EAE. IFNγ is highly expressed by adult donor CD4+ T cells that are adoptively transferred but not by transferred neonate donor cells. In contrast, IL-17 transcripts could not be detected in adult or neonate CNS in this EAE model, and neither adult nor neonate donor CD4+ T cells expressed IL-17 at the time of adoptive transfer.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9036, USA.
authors.forename: Petra D
authors.initials: PD
authors.lastname: Cravens
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
authors.forename: Rehana
authors.initials: R
authors.lastname: Hussain
authors.forename: Emily
authors.initials: E
authors.lastname: Herndon
authors.forename: Benjamine
authors.initials: B
authors.lastname: Arellano
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Ben
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Timmons
authors.forename: Cyd
authors.initials: C
authors.lastname: Castro-Rojas
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
authors.forename: Martin S
authors.initials: MS
authors.lastname: Weber
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002490:Central Nervous System / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D018417:Th1 Cells / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen; C571327:Mog protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D012313:RNA