MHC class II-restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell-mediated autoimmunity.
Although plasmacytoid dendritic cells (pDCs) express major histocompatibility complex class II (MHCII) molecules, and can capture, process, and present antigens (Ags), direct demonstrations that they function as professional Ag-presenting cells (APCs) in vivo during ongoing immune responses remain lacking. We demonstrate that mice exhibiting a selective abrogation of MHCII expression by pDCs develop exacerbated experimental autoimmune encephalomyelitis (EAE) as a consequence of enhanced priming of encephalitogenic CD4(+) T cell responses in secondary lymphoid tissues. After EAE induction, pDCs are recruited to lymph nodes and establish MHCII-dependent myelin-Ag-specific contacts with CD4(+) T cells. These interactions promote the selective expansion of myelin-Ag-specific natural regulatory T cells that dampen the autoimmune T cell response. pDCs thus function as APCs during the course of EAE and confer a natural protection against autoimmune disease development that is mediated directly by their ability to present of Ags to CD4(+) T cells in vivo.
Irla
Magali
M
Department of Pathology, University of Geneva Medical School, 1211 Geneva, Switzerland.
Küpfer
Natalia
N
Suter
Tobias
T
Lissilaa
Rami
R
Benkhoucha
Mahdia
M
Skupsky
Jonathan
J
Lalive
Patrice H
PH
Fontana
Adriano
A
Reith
Walter
W
Hugues
Stéphanie
S
D000818:Animals; D017951:Antigen Presentation; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000949:Histocompatibility Antigens Class II