Transgenic expression of CCL2 in the central nervous system prevents experimental autoimmune encephalomyelitis.
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-gamma. 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.
Elhofy
Adam
A
Department of Pathology, Interdepartmental Immunobiology Center, Institute of Neuroscience, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Wang
Jintang
J
Tani
Mari
M
Fife
Brian T
BT
Kennedy
Kevin J
KJ
Bennett
Jami
J
Huang
Deren
D
Ransohoff
Richard M
RM
Karpus
William J
WJ
D000818:Animals; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; C435023:myelin proteolipid protein (139-151)