The lymphoproliferative defect in CTLA-4-deficient mice is ameliorated by an inhibitory NK cell receptor.

Details

Serval ID
serval:BIB_B53A36E7503C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The lymphoproliferative defect in CTLA-4-deficient mice is ameliorated by an inhibitory NK cell receptor.
Journal
Blood
Author(s)
Chambers C.A., Kang J., Wu Y., Held W., Raulet D.H., Allison J.P.
ISSN
0006-4971
Publication state
Published
Issued date
2002
Peer-reviewed
Oui
Volume
99
Number
12
Pages
4509-4516
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
T-cell responses are regulated by activating and inhibiting signals. CD28 and its homologue, cytotoxic T-lymphocyte antigen 4 (CTLA-4), are the primary regulatory molecules that enhance or inhibit T-cell activation, respectively. Recently it has been shown that inhibitory natural killer (NK) cell receptors (NKRs) are expressed on subsets of T cells. It has been proposed that these receptors may also play an important role in regulating T-cell responses. However, the extent to which the NKRs modulate peripheral T-cell homeostasis and activation in vivo remains unclear. In this report we show that NK cell inhibitory receptor Ly49A engagement on T cells dramatically limits T-cell activation and the resultant lymphoproliferative disorder that occurs in CTLA-4-deficient mice. Prevention of activation and expansion of the potentially autoreactive CTLA-4(-/-) T cells by the Ly49A-mediated inhibitory signal demonstrates that NKR expression can play an important regulatory role in T-cell homeostasis in vivo. These results demonstrate the importance of inhibitory signals in T-cell homeostasis and suggest the common biochemical basis of inhibitory signaling pathways in T lymphocytes.
Keywords
Animals, Antigens, CD, Antigens, Differentiation/genetics, Antigens, Differentiation/immunology, Antigens, Ly, Carrier Proteins/immunology, Carrier Proteins/pharmacology, H-2 Antigens/pharmacology, Homeostasis/immunology, Immunoconjugates, Killer Cells, Natural/immunology, Lectins, C-Type, Lymphocyte Activation/drug effects, Lymphocyte Activation/immunology, Lymphoproliferative Disorders/immunology, Membrane Proteins/immunology, Membrane Proteins/pharmacology, Mice, Mice, Knockout, NK Cell Lectin-Like Receptor Subfamily A, Receptors, Immunologic/immunology, Receptors, NK Cell Lectin-Like, Signal Transduction, T-Lymphocytes/cytology, T-Lymphocytes/drug effects
Pubmed
Web of science
Open Access
Yes
Create date
17/01/2008 15:24
Last modification date
20/08/2019 15:23
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