p150/95 (CD11c/CD18) expression is required for the development of experimental autoimmune encephalomyelitis.
p150/95 (CD11c/CD18, CR4) is a member of the beta(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-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 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-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 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.
Bullard
Daniel C
DC
Department of Microbiology, University of Alabama at Birmingham, 845 19th Street S., Birmingham, AL 35294, USA.
Hu
Xianzhen
X
Adams
Jillian E
JE
Schoeb
Trenton R
TR
Barnum
Scott R
SR
D000818:Animals; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D006023:Glycoproteins / Q000276:immunology; D016167:Integrin alphaXbeta2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D010641:Phenotype; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D006023:Glycoproteins; D016167:Integrin alphaXbeta2; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)