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Review
. 2016 Sep 15;197(6):2045-50.
doi: 10.4049/jimmunol.1601135.

Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway

Andrew B Adams  1 , Mandy L Ford  1 , Christian P Larsen  2
Affiliations
Review

Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway

Andrew B Adams et al. J Immunol. .

Abstract

T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. TCR signaling in the absence of costimulatory signals can lead to an abortive attempt at activation and subsequent anergy. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. The development of the fusion protein CTLA-4-Ig as an experimental and subsequent therapeutic tool is one of the major success stories in modern immunology. Abatacept and belatacept are clinically approved agents for the treatment of rheumatoid arthritis and renal transplantation, respectively. Future interventions may include selective CD28 blockade to block the costimulatory potential of CD28 while exploiting the coinhibitory effects of CTLA-4.

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Figures

FIGURE 1
FIGURE 1
Impact of CTLA-4 Ig versus anti-CD28 domain Abs on alloreactive T cell responses. (A) Alloreactive T cells become activated and differentiate into cytokine-secreting effector T cells (Teffs) upon TCR recognition of alloantigen. Tregs can dampen this response by CTLA-4–mediated competition for CD28 ligands (CD80 and CD86) and by secretion of antiinflammatory cytokines IL-10 and TGF-β. (B) CTLA-4–Ig inhibits Teff function but also impairs Treg survival and suppressive capacity, whereas selective CD28 blockade better inhibits Teff accumulation and function and better maintains Treg suppressor function by preserving CTLA-4–mediated coinhibitory signals.
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References

    1. Haskins K, Kubo R, White J, Pigeon M, Kappler J, Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J Exp Med. 1983;157:1149–1169. - PMC - PubMed
    1. Hedrick SM, Cohen DI, Nielsen EA, Davis MM. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984;308:149–153. - PubMed
    1. Lafferty KJ, Woolnough J. The origin and mechanism of the allograft reaction. Immunol Rev. 1977;35:231–262. - PubMed
    1. Jenkins MK, Schwartz RH. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med. 1987;165:302–319. - PMC - PubMed
    1. June CH, Ledbetter JA, Linsley PS, Thompson CB. Role of the CD28 receptor in T-cell activation. Immunol Today. 1990;11:211–216. - PubMed

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