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PMID: 27192564 Published · ppublish English Journal Article Review

CD28 Costimulation: From Mechanism to Therapy.

Immunity ·Vol. 44 ·No. 5 ·2016-00-17 ·Pages 973-88

Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA

Abstract

Ligation of the CD28 receptor on T cells provides a critical second signal alongside T cell receptor (TCR) ligation for naive T cell activation. Here, we discuss the expression, structure, and biochemistry of CD28 and its ligands. CD28 signals play a key role in many T cell processes, including cytoskeletal remodeling, production of cytokines, survival, and differentiation. CD28 ligation leads to unique epigenetic, transcriptional, and post-translational changes in T cells that cannot be recapitulated by TCR ligation alone. We discuss the function of CD28 and its ligands in both effector and regulatory T cells. CD28 is critical for regulatory T cell survival and the maintenance of immune homeostasis. We outline the roles that CD28 and its family members play in human disease and we review the clinical efficacy of drugs that block CD28 ligands. Despite the centrality of CD28 and its family members and ligands to immune function, many aspects of CD28 biology remain unclear. Translation of a basic understanding of CD28 function into immunomodulatory therapeutics has been uneven, with both successes and failures. Such real-world results might stem from multiple factors, including complex receptor-ligand interactions among CD28 family members, differences between the mouse and human CD28 families, and cell-type specific roles of CD28 family members.

MeSH Terms
Abatacept/therapeutic use Animals Autoimmune Diseases/genetics,immunology,therapy CD28 Antigens/genetics,immunology,metabolism CTLA-4 Antigen/antagonists & inhibitors Homeostasis Humans Immunotherapy/methods,trends Lymphocyte Activation Mice Molecular Targeted Therapy Receptor Cross-Talk Receptors, Antigen, T-Cell/metabolism Signal Transduction T-Lymphocytes/immunology
Chemicals
CD28 Antigens CTLA-4 Antigen CTLA4 protein, human Receptors, Antigen, T-Cell Abatacept
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Esensten Jonathan H
Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA. Electronic address: jonathan.esensten@ucsf.edu.
Helou Ynes A
Division of Rheumatology, Department of Medicine, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, CA 94143, USA.
Chopra Gaurav
Department of Chemistry, Purdue Center for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA.
Weiss Arthur
Division of Rheumatology, Department of Medicine, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Bluestone Jeffrey A
Diabetes Center and Department of Medicine, University of California, San Francisco, CA 94143, USA. Electronic address: jeff.bluestone@ucsf.edu.
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2016.04.020
Email
jonathan.esensten@ucsf.edu
jeff.bluestone@ucsf.edu
Published
2016-00-17
Pages
973-88
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC4932896
Subset
IM
Grants
NIDDK NIH HHS · P30 DK063720 · United States
NIAID NIH HHS · R01 AI114575 · United States
NIAID NIH HHS · R37 AI114575 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2016.04.020 PMC Full Text View journal details
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