Induction of low dose oral tolerance in monocyte chemoattractant protein-1- and CCR2-deficient mice.
The chemokine monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 have been shown to play an important role in the migration and trafficking of macrophages and Th1 effector cells in experimental autoimmune encephalomyelitis. Also, MCP-1 has been reported to regulate oral tolerance induction by inhibition of Th1 cell-related cytokines and by the ability of Abs to MCP-1 to inhibit oral tolerance. This study demonstrates that neither MCP-1 nor its receptor CCR2 is required for the induction of oral tolerance. Mice deletional for either MCP-1 or CCR2 had suppressed cell-proliferative and Th1 responses following oral administration and immunization with myelin oligodendrocyte glycoprotein (MOG(35-55)). TGF-beta was up-regulated in fed and immunized deletional mice, while IL-4 was absent from deletional mice, but up-regulated in controls. Decreased experimental autoimmune encephalomyelitis severity was found in MOG(35-55)-fed MCP-1 deletional mice, indicating induction of oral tolerance. These results demonstrate that MCP-1 is not required for induction of oral tolerance and that MCP-1 and CCR2 are essential for up-regulation of IL-4 in tolerized mice.
Gonnella
Patricia A
PA
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. patricia.gonnella@tch.harvard.edu
Kodali
Dhatri
D
Weiner
Howard L
HL
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics*; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D015847:Interleukin-4 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D008221:Lymphoid Tissue / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C445081:myelin oligodendrocyte glycoprotein (35-55); D015847:Interleukin-4