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J. Exp. Med.,
Volume 187, Number 5, March 2, 1998 733-741
By
From the * Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, and
Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611; and 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.
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109
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