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PMID: 21488898 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family.

Immunological reviews ·Vol. 241 ·No. 1 ·2011-05-00 ·Pages 180-205

Bour-Jordan H, Esensten JH, Martinez-Llordella M, Penaranda C, Stumpf M, Bluestone JA

Abstract

Positive and negative costimulation by members of the CD28 family is critical for the development of productive immune responses against foreign pathogens and their proper termination to prevent inflammation-induced tissue damage. In addition, costimulatory signals are critical for the establishment and maintenance of peripheral tolerance. This paradigm has been established in many animal models and has led to the development of immunotherapies targeting costimulation pathways for the treatment of cancer, autoimmune disease, and allograft rejection. During the last decade, the complexity of the biology of costimulatory pathways has greatly increased due to the realization that costimulation does not affect only effector T cells but also influences regulatory T cells and antigen-presenting cells. Thus, costimulation controls T-cell tolerance through both intrinsic and extrinsic pathways. In this review, we discuss the influence of costimulation on intrinsic and extrinsic pathways of peripheral tolerance, with emphasis on members of the CD28 family, CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and programmed death-1 (PD-1), as well as the downstream cytokine interleukin-1 (IL-2).

MeSH Terms
Animals Antigen-Presenting Cells/immunology Antigens, CD/immunology Apoptosis Regulatory Proteins/immunology Autoimmune Diseases/immunology,therapy B7-1 Antigen/immunology CD28 Antigens/immunology CTLA-4 Antigen Graft Rejection/immunology,therapy Humans Immune Tolerance Immunotherapy/trends Neoplasms/immunology,therapy Programmed Cell Death 1 Receptor Receptor Cross-Talk T-Lymphocyte Subsets/immunology T-Lymphocytes, Regulatory/immunology
Chemicals
Antigens, CD Apoptosis Regulatory Proteins B7-1 Antigen CD28 Antigens CTLA-4 Antigen CTLA4 protein, human PDCD1 protein, human Programmed Cell Death 1 Receptor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bour-Jordan Hélène
UCSF Diabetes Center, University of California at San Francisco, San Francisco, CA 94143-0400, USA.
Esensten Jonathan H
Martinez-Llordella Marc
Penaranda Cristina
Stumpf Melanie
Bluestone Jeffrey A
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Article Info
Journal
Immunological reviews
Abbr.
Immunol Rev
ISSN
1600-065X
DOI
10.1111/j.1600-065X.2011.01011.x
Published
2011-05-00
Pages
180-205
Language
English
Region
England
NLM ID
7702118
PMCID
PMC3077803
Subset
IM
Grants
NIDDK NIH HHS · P30 DK063720 · United States
NIAID NIH HHS · R37 AI046643 · United States
NIDDK NIH HHS · P30 DK063720-01 · United States
NIAID NIH HHS · R37 AI046643-11 · United States
NIAID NIH HHS · P01 AI035294-08 · United States
NIAID NIH HHS · R01 AI050834-10 · United States
NIAID NIH HHS · R01 AI050834 · United States
External Links
PubMed source DOI: 10.1111/j.1600-065X.2011.01011.x PMC Full Text View journal details
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