The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article
Right arrow Full Text
Right arrow Full Text (PDF, 117K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Karpus, W. J.
Right arrow Articles by Lukacs, N. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Karpus, W. J.
Right arrow Articles by Lukacs, N. W.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1998/3/733/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 5, March 2, 1998 733-741


Articles

Monocyte Chemotactic Protein 1 Regulates Oral Tolerance Induction by Inhibition of T Helper Cell 1–related Cytokines

William J. Karpus*, Kevin J. Kennedy*, Steven L. Kunkel{ddagger}, and Nicholas W. Lukacs{ddagger}

From the * Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611; and {ddagger} Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109

Experimental autoimmune encephalomyelitis (EAE) is a T cell–mediated autoimmune demyelinating disease of the central nervous system that serves as an animal model for multiple sclerosis. Antigen-specific tolerance regimens, including oral tolerance, have been used prophylactically to prevent development of acute EAE as well as a number of other autoimmune diseases. Two mechanisms have been proposed to explain the immunologic basis for disease inhibition: bystander immune suppression and clonal anergy/deletion. This report demonstrates a novel mechanism for monocyte chemotactic protein (MCP)-1 as a regulatory factor of oral tolerance. Oral administration of proteolipid protein peptide (PLP139–151) increased MCP-1 expression in the intestinal mucosa, Peyer's patch, and mesenteric lymph nodes. Increase in MCP-1 expression resulted in downregulation of mucosal interleukin (IL)-12 expression with concomitant increase in mucosal IL-4 expression. Functionally, MCP-1 upregulation was shown to regulate oral tolerance induction by the ability of antibodies to MCP-1 to inhibit tolerance induction. The anti–MCP-1 abrogation of oral tolerance induction also resulted in restoration of mucosal IL-12 expression as well as peripheral antigen-specific T helper cell 1 responses. These results demonstrate a novel and important role for MCP-1 in the regulation or oral tolerance for the prevention and treatment of autoimmune disease.


This work was supported by National Institutes of Health AI-35934 and NS-34510 to W.J. Karpus.

Address correspondence to William J. Karpus, Department of Pathology, Northwestern University Medical School, 303 E. Chicago Ave., W127, Chicago, IL 60611. Phone: 312-503-1005; Fax: 312-503-8240; E-mail: w-karpus{at}nwu.edu

1 Abbreviations used in this paper: CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; MCP, monocyte chemotactic protein; MIP, macrophage inflammatory protein; MLN, mesenteric lymph node; MS, multiple sclerosis; NRS, normal rabbit serum; PLP, proteolipid protein; RANTES, regulated on activation normal T cell expressed and secreted; RT, reverse transcriptase.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS