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PMID: 11602646 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dendritic cell maturation overrules H-2D-mediated natural killer T (NKT) cell inhibition: critical role for B7 in CD1d-dependent NKT cell interferon gamma production.

The Journal of experimental medicine ·Vol. 194 ·No. 8 ·2001-10-15 ·Pages 1179-86

Ikarashi Y, Mikami R, Bendelac A, Terme M, Chaput N, Terada M, Tursz T, Angevin E, Lemonnier FA, Wakasugi H, Zitvogel L

Abstract

Given the broad expression of H-2 class Ib molecules on hematopoietic cells, antigen presentation pathways among CD1d expressing cells might tightly regulate CD1d-restricted natural killer T (NKT) cells. Bone marrow-derived dendritic cells (BM-DCs) and not adherent splenocytes become capable of triggering NK1.1(+)/T cell receptor (TCR)(int) hepatic NKT cell activation when (a) immature BM-DCs lack H-2D(b)-/- molecules or (b) BM-DCs undergo a stress signal of activation. In such conditions, BM-DCs promote T helper type 1 predominant CD1d-restricted NKT cell stimulation. H-2 class Ia-mediated inhibition involves more the direct H-2D(b) presentation than the indirect Qa-1(b) pathway. Such inhibition can be overruled by B7/CD28 interactions and marginally by CD40/CD40L or interleukin 12. These data point to a unique regulatory role of DCs in NKT cell innate immune responses and suggest that H-2 class Ia and Ib pathways differentially control NKT cell recognition of DC antigens.

MeSH Terms
Animals Antigens/genetics,immunology Antigens, CD1/genetics,immunology Antigens, CD1d Antigens, Ly Antigens, Surface B7-1 Antigen/immunology Bone Marrow Cells/cytology,immunology CD28 Antigens/immunology Cell Differentiation Cells, Cultured Dendritic Cells/cytology,immunology Female H-2 Antigens/genetics,immunology Histocompatibility Antigen H-2D Interferon-gamma/biosynthesis Killer Cells, Natural/immunology Lectins, C-Type Mice Mice, Inbred C57BL Mice, Knockout NK Cell Lectin-Like Receptor Subfamily B Proteins/genetics,immunology Receptors, Antigen, T-Cell, alpha-beta/immunology Signal Transduction/immunology T-Lymphocytes/immunology
Chemicals
Antigens Antigens, CD1 Antigens, CD1d Antigens, Ly Antigens, Surface B7-1 Antigen CD28 Antigens H-2 Antigens Histocompatibility Antigen H-2D Klrb1c protein, mouse Lectins, C-Type NK Cell Lectin-Like Receptor Subfamily B Proteins Receptors, Antigen, T-Cell, alpha-beta Interferon-gamma
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Ikarashi Y
Unité d'Immunologie, Département de Biologie Clinique, Institut Gustave Roussy, 94805 Villejuif Cedex, France.
Mikami R
Bendelac A
Terme M
Chaput N
Terada M
Tursz T
Angevin E
Lemonnier F A
Wakasugi H
Zitvogel L
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.194.8.1179
Published
2001-10-15
Pages
1179-86
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193518
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1084/jem.194.8.1179 PMC Full Text View journal details
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