Published online before print April 13, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.061016

Article

p150/95 (CD11c/CD18) Expression Is Required for the Development of Experimental Autoimmune Encephalomyelitis

Daniel C. Bullard^*, Xianzhen Hu, Jillian E. Adams, Trenton R. Schoeb^*, and Scott R. Barnum^@

From the Departments of Genetics,* Microbiology, and Neurology, University of Alabama at Birmingham, Birmingham, Alabama

^@ To whom correspondence should be addressed. E-mail: sbarnum{at}uab.edu.

	Abstract

p150/95 (CD11c/CD18, CR4) is a member of the ₂-integrin family of adhesion molecules and is considered an important phagocytic receptor. The role of p150/95 in the development of central nervous system demyelinating diseases, including multiple sclerosis, remains unexplored. To determine p150/95-mediated mechanisms in experimental autoimmune encephalomyelitis (EAE), we performed EAE using CD11c-deficient (CD11c^-/-) mice. EAE in CD11c^-/- mice was significantly attenuated and characterized by markedly reduced spinal cord T-cell infiltration and interferon- production by these cells. Adoptive transfer of antigen-restimulated T cells from wild-type to CD11c^-/- mice produced significantly attenuated EAE, whereas transfer of CD11c^-/- antigen-restimulated T cells to control mice induced a very mild, monophasic EAE. T cells from MOG_35-55 peptide-primed CD11c^-/- mice displayed an unusual cytokine phenotype with elevated levels of interleukin (IL)-2, IL-4, and IL-12 but reduced levels of interferon-, tumor necrosis factor-, IL-10, IL-17, and transforming growth factor- compared with control mice. Overall, CD11c^-/- T cells from primed mice proliferated comparably to that of control T cells on MOG_35-55 restimulation. Our results indicate that expression of p150/95 is critical on both T cells as well as other leukocytes for the development of demyelinating disease and may represent a novel therapeutic target for multiple sclerosis.

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