A paradoxical role of APCs in the induction of intravenous tolerance in experimental autoimmune encephalomyelitis.
The central role of T cells in the induction of tolerance to autoantigens has been well documented. However, the role of antigen-presenting cells (APCs) in this process is not yet fully understood. To better understand the contribution of APCs in tolerance, we studied the interaction of purified APCs and CD4(+) T cells in a model of intravenous (i.v.) tolerance to experimental autoimmune encephalomyelitis (EAE). As expected, we found that T cells were tolerized to the autoantigen after i.v. injection. However, purified APCs obtained from MOG-i.v.-treated mice were paradoxically immuno-stimulatory, as they induced a non-specific Th1-type response both in vitro and in vivo. We conclude that blocking such APC activation would enhance the effectiveness of tolerance induction.
Zhang
Guang-Xian
GX
Department of Neurology, Thomas Jefferson University, 300 JHN Building, 900 Walnut Street, Philadelphia, PA 19107, USA. guang-xian.zhang@jefferson.edu
Yu
Shuo
S
Li
Yonghai
Y
Ventura
Elvira S
ES
Gran
Bruno
B
Rostami
Abdolmohamad
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques / Q000379:methods; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006023:Glycoproteins; D007108:Immune Tolerance / Q000502:physiology*; D007116:Immunization, Passive; D007275:Injections, Intravenous / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D013997:Time Factors
D016207:Cytokines; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; D018121:Receptors, Cytokine; C445081:myelin oligodendrocyte glycoprotein (35-55)