IL-12 driven upregulation of P-selectin ligand on myelin-specific T cells is a critical step in an animal model of autoimmune demyelination.
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system. IL-12p40 monokines play a critical role in the generation of EAE-inducing CD4+T cells. Here we show that IL-12 directly upregulates the expression of the adhesion molecule, P-selectin glycoprotein ligand (PSGL-1), on B10.PL MBP-TCR transgenic T cells during their initial encounter with antigen. Pre-incubation of IL-12-stimulated myelin-reactive CD4+T cells with a blocking antibody against PSGL-1 reduced the incidence and severity of EAE. We conclude that IL-12-driven PSGL-1 expression can facilitate the development of autoimmune demyelination.
Deshpande
Pratima
P
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 605, Rochester, NY, 14642, USA.
King
Irah L
IL
Segal
Benjamin M
BM
D019264:Adoptive Transfer; D000818:Animals; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018664:Interleukin-12 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; C084882:P-selectin ligand protein; D018664:Interleukin-12