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PMID: 19426212 Published · ppublish English Journal Article Review

CD28 and CTLA-4 coreceptor expression and signal transduction.

Immunological reviews ·Vol. 229 ·No. 1 ·2009-05-00 ·Pages 12-26

Rudd CE, Taylor A, Schneider H

Abstract

T-cell activation is mediated by antigen-specific signals from the TCRzeta/CD3 and CD4-CD8-p56lck complexes in combination with additional co-signals provided by coreceptors such as CD28, inducible costimulator (ICOS), cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death (PD-1), and others. CD28 and ICOS provide positive signals that promote and sustain T-cell responses, while CTLA-4 and PD-1 limit responses. The balance between stimulatory and inhibitory co-signals determines the ultimate nature of T-cell responses where response to foreign pathogen is achieved without excess inflammation and autoimmunity. In this review, we outline the current knowledge of the CD28 and CTLA-4 signaling mechanisms [involving phosphatidylinositol 3 kinase (PI3K), growth factor receptor-bound protein 2 (Grb2), Filamin A, protein kinase C theta (PKCtheta), and phosphatases] that control T-cell immunity. We also present recent findings on T-cell receptor-interacting molecule (TRIM) regulation of CTLA-4 surface expression, and a signaling pathway involving CTLA-4 activation of PI3K and protein kinase B (PKB)/AKT by which cell survival is ensured under conditions of anergy induction.

MeSH Terms
3-Phosphoinositide-Dependent Protein Kinases Adaptor Proteins, Signal Transducing/immunology,metabolism Animals Antigens, CD/immunology,metabolism Antigens, Differentiation, T-Lymphocyte/immunology,metabolism CD28 Antigens/immunology,metabolism CTLA-4 Antigen Contractile Proteins/immunology,metabolism Filamins Humans Inducible T-Cell Co-Stimulator Protein Lymphocyte Activation/immunology Microfilament Proteins/immunology,metabolism Phosphatidylinositol 3-Kinases/immunology,metabolism Protein Serine-Threonine Kinases/immunology,metabolism Signal Transduction/immunology T-Lymphocytes/immunology,metabolism
Chemicals
Adaptor Proteins, Signal Transducing Antigens, CD Antigens, Differentiation, T-Lymphocyte CD28 Antigens CTLA-4 Antigen CTLA4 protein, human Contractile Proteins Filamins ICOS protein, human Inducible T-Cell Co-Stimulator Protein Microfilament Proteins 3-Phosphoinositide-Dependent Protein Kinases Protein Serine-Threonine Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Rudd Christopher E
Department of Pathology, Cell Signalling Section, University of Cambridge, Cambridge, UK. [email protected]
Taylor Alison
Schneider Helga
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Article Info
Journal
Immunological reviews
Abbr.
Immunol Rev
ISSN
1600-065X
DOI
10.1111/j.1600-065X.2009.00770.x
Email
[email protected]
Published
2009-05-00
Pages
12-26
Language
English
Region
England
NLM ID
7702118
PMCID
PMC4186963
Subset
IM
Grants
Wellcome Trust · 060111 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/E015395/1 · United Kingdom
External Links
PubMed source DOI: 10.1111/j.1600-065X.2009.00770.x PMC Full Text View journal details
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