p150/95 (CD11c/CD18) Expression Is Required for the Development of
Experimental Autoimmune Encephalomyelitis.
From the Departments of Genetics,* Microbiology, and
Neurology, University of Alabama at Birmingham, Birmingham, Alabama.
p150/95 (CD11c/CD18, CR4) is a member of the beta2-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-gamma 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 MOG35-55 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-gamma, tumor necrosis factor-alpha, IL-10,
IL-17, and transforming growth factor-beta compared with control mice. Overall,
CD11c(-/-) T cells from primed mice proliferated comparably to that of control T
cells on MOG35-55 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.
PMID: 17434965 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17434965&itool=pubmed_DocSum
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