Antigen-oriented T cell migration contributes to myelin peptide induced-EAE and immune tolerance.
Treatment with soluble myelin peptide can efficiently and specifically induce tolerance to demyelination autoimmune diseases including multiple sclerosis, however the mechanism underlying this therapeutic effect remains to be elucidated. In actively induced mouse model of experimental autoimmune encephalomyelitis (EAE) we analyzed T cell and innate immune cell responses in the central nervous system (CNS) and spleen after intraperitoneal (i.p.) infusion of myelin oligodendrocyte glycoprotein (MOG). We found that i.p. MOG infusion blocked effector T cell recruitment to the CNS and protected mice from EAE and lymphoid organ atrophy. Innate immune CD11b(+) cells preferentially recruited MOG-specific effector T cells, particularly when activated to become competent antigen presenting cells (APCs). During EAE development, mature APCs were enriched in the CNS rather than in the spleen, attracting effector T cells to the CNS. Increased myelin antigen exposure induced CNS-APC maturation, recruiting additional effector T cells to the CNS, causing symptoms of disease. MOG triggered functional maturation of splenic APCs. MOG presenting APCs interacted with MOG-specific T cells in the spleen, aggregating to cluster around CD11b(+) cells, and were trapped in the periphery. This process was MHC II dependent as an MHC II directed antibody blocked CD4(+) T cell cluster formation. These findings highlight the role of myelin peptide-loaded APCs in myelin peptide-induced EAE and immune tolerance.
Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Clinical Laboratory of Henan Province, PR China.
Peiguo
P
Zheng
Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Clinical Laboratory of Henan Province, PR China.
Hanxiao
H
Fu
Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Clinical Laboratory of Henan Province, PR China.
Gaohui
G
Wei
Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Clinical Laboratory of Henan Province, PR China.
Zhongwei
Z
Wei
Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Clinical Laboratory of Henan Province, PR China.
Junhua
J
Zhang
Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Clinical Laboratory of Henan Province, PR China.
Xuehan
X
Ma
Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Clinical Laboratory of Henan Province, PR China.
Dong
D
Rui
Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Clinical Laboratory of Henan Province, PR China.
Xianchun
X
Meng
Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Clinical Laboratory of Henan Province, PR China. Electronic address: mingliang@zzu.edu.cn.
Liang
L
Ming
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)
Experimental autoimmune encephalomyelitis; Immune tolerance; T-cell migration