Costimulation blockade in autoimmunity and transplantation: the CD28 pathway

Andrew B. Adams, Mandy L. Ford, Christian P. Larsen

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

T cell activation is a complex process that requiresmultiple 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.

Original languageEnglish (US)
Pages (from-to)2045-2050
Number of pages6
JournalJournal of Immunology
Volume197
Issue number6
DOIs
StatePublished - Sep 15 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grants R37 AI040519 (to C.P.L.), U19 AI051731 (to C.P.L. and A.B.A.), and R01 AI104699 and R01 AI073707 (to M.L.F.).

Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.

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