4.7 Article

The Peyer's patch is a critical immunoregulatory site for mucosal tolerance in experimental autoimmune encephalomylelitis (EAE)

Journal

JOURNAL OF AUTOIMMUNITY
Volume 30, Issue 4, Pages 230-237

Publisher

ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2007.10.002

Keywords

autoimmunity; EAE/MS; tolerance; T cell receptors; Peyer's patch

Categories

Funding

  1. NIAID NIH HHS [R01 AI043376-02, R01 AI043376-03, AI 35960, R01 AI043376-05, R01 AI043376-04, R01 AI064320-01A1, R01 AI064320] Funding Source: Medline
  2. NINDS NIH HHS [NS 23561, R01 NS048316-01, R01 NS048316] Funding Source: Medline
  3. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI043376, R01AI035960, R01AI064320] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS048316, R01NS023561] Funding Source: NIH RePORTER

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Expression of MCP-1 in the central nervous system (CNS) is associated with various neuroinflammatory diseases, including multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In this study, we found that MCP-1 was decreased in the CNS but increased in the gut following oral administration of myelin basic protein (MBP) correlating with protection from EAE. To study the trafficking and the fate of T cells during oral tolerance, MBP-specific TCR transgenic (Tg) CD4(+) T cells were labeled using 5,6-carboxy-succinimidyl-fluorescein-ester (CFSE) and transferred intravenously to syngeneic B10.PL recipients before feeding with either MBP or PBS. We observed that the CFSE-labeled T cells traffic to the peripheral lymphoid tissue and the Peyer's patches (PP). The labeled T cells proliferate in vivo in both the lymph node and the PP 48 h after MBP feeding, but the cells are maintained in the PP longer than in the LN. CFSE-labeled cells in the PP have high levels of CD69 and Fas expression which is accompanied by increased apoptosis after MBP feeding. Our observations suggest that oral administration of autoantigen induces an elevation of MCP-1 in the gut, early T cell trafficking and activation in the periphery and the PP, followed by deletion of autoreactive T cells in the PP. (C) 2007 Elsevier Ltd. All rights reserved.

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