Presentation of the self antigen myelin basic protein by dendritic cells leads to experimental autoimmune encephalomyelitis.
Bone marrow (BM)-derived dendritic cells (DC) are potent stimulators of naive CD4+ T cell activation. Because DC are efficient at Ag processing and could potentially present self Ags, we investigated the role of DC in the presentation of an encephalitogenic peptide from myelin basic protein (Ac1-11) in the induction of experimental autoimmune encephalomyelitis (EAE). To determine if DC could prime for EAE, we transferred DC pulsed with Ac1-11 or with medium alone into irradiated mice in combination with CD4+ T cells isolated from a mouse transgenic for a TCR specific for Ac1-11 + I-Au. Mice transferred with Ac1-11-pulsed DC developed EAE 7-10 days later, whereas mice receiving medium-pulsed DC did not. By day 15, all mice given peptide-loaded DC had signs of tail and hind limb paralysis, and by day 20 infiltration of Ac1-11-specific CD4+ T cells was detected in the brain parenchyma. We also demonstrated interactions between Ac1-11-pulsed DC and Ac1-11-specific T cells in the lymph nodes 24 h following adoptive transfer of both cell populations. These data show that DC can efficiently present the self Ag myelin basic protein Ac1-11 to Ag-specific T cells in the periphery of mice to induce EAE.
Dittel
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Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06510, USA. bonnie.dittel@yale.edu
Visintin
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I
Merchant
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Janeway
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CA
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013116:Spinal Cord / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell