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Open Access Research

The neonatal CNS is not conducive for encephalitogenic Th1 T cells and B cells during experimental autoimmune encephalomyelitis

Petra D Cravens1, Bernd C Kieseier2, Rehana Hussain1, Emily Herndon3, Benjamine Arellano1, Li-Hong Ben1, Brenda C Timmons4, Cyd Castro-Rojas1, Hans-Peter Hartung2, Bernhard Hemmer5, Martin S Weber567, Scott S Zamvil89* and Olaf Stüve11025*

Author Affiliations

1 Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390-9036, USA

2 Department of Neurology, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany

3 Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390, USA

4 Hamon Center for Therapeutic Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390, USA

5 Department of Neurology, Klinikum rechts der Isar, Technische Universität München, München, 81675, Germany

6 Department of Neurology, University Medical Center, Georg August University, Göttingen, 37075, Germany

7 Department of Neuropathology, University Medical Center, Georg August University, Göttingen, 37975, Germany

8 Department of Neurology, University of California, San Francisco, CA, 94143, USA

9 Program in Immunology, University of California, San Francisco, CA, 94143, USA

10 Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Rd, Dallas, TX, 75216, USA

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Journal of Neuroinflammation 2013, 10:67  doi:10.1186/1742-2094-10-67

Published: 24 May 2013

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.

Keywords:
Age; Antigen presentation; Autoimmunity; Development; EAE; Experimental autoimmune encephalomyelitis; Human; Lymphocytes; Major histocompatibility complex; MHC; MS; Mouse; Multiple sclerosis; Rodent; T helper cells 17