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Transgenic expression of CCL2 in the central nervous system prevents experimental autoimmune encephalomyelitis
Author(s) -
Elhofy Adam,
Wang Jintang,
Tani Mari,
Fife Brian T.,
Kennedy Kevin J.,
Bennett Jami,
Huang DeRen,
Ransohoff Richard M.,
Karpus William J.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0804465
Subject(s) - biology , experimental autoimmune encephalomyelitis , ccr2 , chemokine , ccl2 , transgene , genetically modified mouse , immunology , glial fibrillary acidic protein , monocyte , microbiology and biotechnology , chemokine receptor , immune system , immunohistochemistry , biochemistry , gene
CC chemokine ligand 2 (CCL2)/monocyte chemotactic protein‐1, a member of the CC chemokine family, is a chemoattractant for monocytes and T cells through interaction with its receptor CCR2. In the present study, we examined a T helper cell type 1 (Th1)‐dependent disease, proteolipid protein‐induced experimental autoimmune encephalomyelitis, in a transgenic mouse line that constitutively expressed low levels of CCL2 in the central nervous system (CNS) under control of the astrocyte‐specific glial fibrillary acidic protein promoter. CCL2 transgenic mice developed significantly milder clinical disease than littermate controls. As determined by flow cytometry, mononuclear cell infiltrates in the CNS tissues of CCL2 transgenic and littermate‐control mice contained equal numbers of CD4 + and CD8 + T cells, and the CCL2 transgenic mice showed an enhanced number of CNS‐infiltrating monocytes. CNS antigen‐specific T cells from CCL2 transgenic mice produced markedly less interferon‐γ. Overexpression of CCL2 in the CNS resulted in decreased interleukin‐12 receptor expression by antigen‐specific T cells. Collectively, these results indicate that sustained, tissue‐specific expression of CCL2 in vivo down‐regulates the Th1 autoimmune response, culminating in milder clinical disease.