CD11c+CD11b+ dendritic cells play an important role in intravenous tolerance and the suppression of experimental autoimmune encephalomyelitis.
The central role of T cells in the induction of immunological tolerance against i.v. Ags has been well documented. However, the role of dendritic cells (DCs), the most potent APCs, in this process is not clear. In the present study, we addressed this issue by examining the involvement of two different DC subsets, CD11c(+)CD11b(+) and CD11c(+)CD8(+) DCs, in the induction of i.v. tolerance. We found that mice injected i.v. with an autoantigen peptide of myelin oligodendrocyte glycoprotein (MOG) developed less severe experimental autoimmune encephalomyelitis (EAE) following immunization with MOG peptide but presented with more CD11c(+)CD11b(+) DCs in the CNS and spleen. Upon coculturing with T cells or LPS, these DCs exhibited immunoregulatory characteristics, including increased production of IL-10 and TGF-beta but reduced IL-12 and NO; they were also capable of inhibiting the proliferation of MOG-specific T cells and enhancing the generation of Th2 cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells. Furthermore, these DCs significantly suppressed ongoing EAE upon adoptive transfer. These results indicate that CD11c(+)CD11b(+) DCs, which are abundant in the CNS of tolerized animals, play a crucial role in i.v. tolerance and EAE and may be a candidate cell population for immunotherapy of autoimmune diseases.
Li
Hongmei
H
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Zhang
Guang-Xian
GX
Chen
Youhai
Y
Xu
Hui
H
Fitzgerald
Denise C
DC
Zhao
Zhao
Z
Rostami
Abdolmohamad
A
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis*; D039521:CD11c Antigen / Q000096:biosynthesis*; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D007108:Immune Tolerance; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D008907:Mink; D008969:Molecular Sequence Data; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
D039481:CD11b Antigen; D039521:CD11c Antigen; D016827:CD8 Antigens