CD43 modulates severity and onset of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis characterized by infiltration of activated CD4(+) T lymphocytes into tissues of the CNS. This study investigated the role of CD43 in the induction and progression of EAE. Results demonstrate that CD43-deficient mice have reduced and delayed clinical and histological disease severity relative to CD43(+/+) mice. This reduction was characterized by decreased CD4(+) T cell infiltration of the CNS of CD43(-/-) mice but similar numbers of Ag-specific T cells in the periphery, suggesting a defect in T cell trafficking to the CNS. The absence of CD43 also affected cytokine production, as myelin oligodendrocyte glycoprotein (MOG) 35-55-specific CD43(-/-) CD4(+) T cells exhibited reduced IFN-gamma and increased IL-4 production. CD43(-/-) CD4(+) MOG-primed T cells exhibited reduced encephalitogenicity relative to CD43(+/+) cells upon adoptive transfer into naive recipients. These results suggest a role for CD43 in the differentiation and migration of MOG(35-55)-specific T cells in EAE, and identify it as a potential target for therapeutic intervention.
Ford
Mandy L
ML
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Onami
Thandi M
TM
Sperling
Anne I
AI
Ahmed
Rafi
R
Evavold
Brian D
BD
D000276:Adjuvants, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D015994:Incidence; D051917:Leukosialin; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D051917:Leukosialin; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55)