CD43 modulates severity and onset of experimental autoimmune encephalomyelitis

J Immunol. 2003 Dec 15;171(12):6527-33. doi: 10.4049/jimmunol.171.12.6527.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / deficiency
  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / physiology*
  • Adoptive Transfer
  • Amino Acid Sequence
  • Animals
  • Antigens, CD*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Disease Progression
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control
  • Epitopes, T-Lymphocyte / immunology
  • Glycoproteins / immunology
  • Incidence
  • Leukosialin
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Molecular Sequence Data
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments / immunology
  • Severity of Illness Index
  • Sialoglycoproteins / deficiency
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / physiology*

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Glycoproteins
  • Leukosialin
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Sialoglycoproteins
  • Spn protein, mouse
  • myelin oligodendrocyte glycoprotein (35-55)