Antigen Presentation in the CNS by Myeloid Dendritic Cells Drives Progression of Relapsing Experimental Autoimmune Encephalomyelitis

: Chronic progression of relapsing experimental autoimmune encephalomyelitis (R‐EAE), a mouse model of multiple sclerosis (MS), is dependent on the activation of T cells to endogenous myelin epitopes, that is, epitope spreading. This review focuses on the cellular and molecular mechanisms underlyin...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Annals of the New York Academy of Sciences Ročník 1103; číslo 1; s. 179 - 191
Hlavní autori:	MILLER, STEPHEN D., McMAHON, EILEEN J., SCHREINER, BETTINA, BAILEY, SAMANTHA L.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Malden, USA Blackwell Publishing Inc 01.04.2007
Predmet:	Animals antigen presentation central nervous system Central Nervous System - immunology Chronic Disease dendritic cells Dendritic Cells - immunology Disease Models, Animal Disease Progression Encephalomyelitis, Autoimmune, Experimental - immunology epitope spreading Epitopes - immunology experimental autoimmune encephalomyelitis Mice Mice, Inbred Strains Models, Immunological multiple sclerosis Multiple Sclerosis - immunology Recurrence
ISSN:	0077-8923, 1749-6632, 1930-6547
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	: Chronic progression of relapsing experimental autoimmune encephalomyelitis (R‐EAE), a mouse model of multiple sclerosis (MS), is dependent on the activation of T cells to endogenous myelin epitopes, that is, epitope spreading. This review focuses on the cellular and molecular mechanisms underlying the process of epitope spreading. Surprisingly, activation of naïve T cells to endogenous myelin epitopes in SJL mice undergoing R‐EAE occurs directly in the central nervous system (CNS), a site generally perceived to be immunologically privileged. Determination of the antigen presentation capacity of antigen‐presenting cell (APC) populations purified from the CNS of mice with established R‐EAE shows that peripherally derived CD11b+CD11c+CD45hi myeloid dendritic cells (mDCs) most efficiently present endogenous myelin antigens to activate both preactivated effector myelin‐specific T cells and naïve T cells. The mDCs, which drive epitope spreading, preferentially polarize pathogenic Th17 responses correlating with their enhanced expression of TGF‐β1, IL‐6, and IL‐23. Both B220+CD11c+ plasmacytoid (pDCs) and CD8α+CD11c+ (CD8 DCs) were superior to CD11b+CD11c–CD45hi macrophages, but less efficient than mDCs at presenting endogenous peptide to induce Th17 cells. In contrast, CNS‐resident CD11b+CD11c–CD45low microglia purified from the inflamed CNS were found to be largely incapable of activating either naïve or effector T cells.
Bibliografia:	ArticleID:NYAS23 ark:/67375/WNG-VDN170VB-F istex:768CFB17612F4A12DC38FAC1262781BE32AD908D ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0077-8923 1749-6632 1930-6547
DOI:	10.1196/annals.1394.023