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J Immunol. 2005 Nov 15;175(10):6327-33.

Critical requirement of CD11b (Mac-1) on T cells and accessory cells for development of experimental autoimmune encephalomyelitis.

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1
Department of Genetics, University of Alabama at Birmingham, 35294, USA.

Abstract

Mac-1 (CD18/CD11b) is a member of the beta2-integrin family of adhesion molecules and is implicated in the development of many inflammatory diseases. The role of Mac-1 in the development of CNS demyelinating diseases, including multiple sclerosis, is not understood, and Ab inhibition studies in experimental allergic encephalomyelitis (EAE), the animal model for multiple sclerosis, have produced conflicting findings. To clarify these results and to determine Mac-1-mediated mechanisms in EAE, we performed EAE using Mac-1-deficient mice. Mac-1 homozygous-deficient, but not Mac-1 heterozygous-deficient mice, had significantly delayed onset and attenuated EAE. Leukocyte infiltration was similar in both groups of mice in early disease but significantly reduced in spinal cords of receptor-deficient mice in late disease. Adoptive transfer of Ag-restimulated T cells from wild-type to Mac-1-deficient mice produced significantly attenuated EAE, whereas transfer of Mac-1-deficient Ag-restimulated T cells to control mice failed to induce EAE. T cells from myelin oligodendrocyte glycoprotein (MOG)35-55 peptide-primed Mac-1-deficient mice displayed an altered cytokine phenotype with elevated levels of TGF-beta and IL-10, but reduced levels of IL-2, IFN-gamma, TNF-alpha, IL-12, and IL-4 compared with control mice. Mac-1-deficient T cells from primed mice proliferated comparably to that of control T cells on MOG35-55 restimulation in vitro. However, the draining lymph nodes of MAC-1-deficient mice on day 10 after MOG35-55 immunization contained lower frequency of blast T cells than in control mice, suggesting poor priming. Our results indicate that Mac-1 expression is critical on both phagocytic cells and T cells for the development of demyelinating disease.

PMID:
16272284
[Indexed for MEDLINE]
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