Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2016 Sep 4

PMID 27591335

Citations 43

Authors

Andrew B Adams

Mandy L Ford

Christian P Larsen

Affiliations

Soon will be listed here.

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.

Citing Articles

Allogeneic Hematopoietic Stem Cell Transplantation After Solid Organ Transplantation in Patients With Hematologic Malignancies Managed With Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis.

Jang C, Hsu J J Hematol. 2024; 13(5):250-258.

PMID: 39493605 PMC: 11526586. DOI: 10.14740/jh1327.

Unlocking Transplant Tolerance with Biomaterials.

Pham J, Coronel M Adv Healthc Mater. 2024; 14(5):e2400965.

PMID: 38843866 PMC: 11834385. DOI: 10.1002/adhm.202400965.

Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells.

Mowery C, Freimer J, Chen Z, Casani-Galdon S, Umhoefer J, Arce M Nat Genet. 2024; 56(6):1156-1167.

PMID: 38811842 PMC: 11176074. DOI: 10.1038/s41588-024-01743-5.

Unique vulnerability of RAC1-mutant melanoma to combined inhibition of CDK9 and immune checkpoints.

Cannon A, Budagyan K, Uribe-Alvarez C, Kurimchak A, Araiza-Olivera D, Cai K Oncogene. 2024; 43(10):729-743.

PMID: 38243078 PMC: 11157427. DOI: 10.1038/s41388-024-02947-z.

Costimulatory Blockade and Solid Organ Transplantation: The Past, Present, and Future.

Kitchens W, Larsen C, Badell I Kidney Int Rep. 2023; 8(12):2529-2545.

PMID: 38106575 PMC: 10719580. DOI: 10.1016/j.ekir.2023.08.037.

References

Linsley P, Wallace P, Johnson J, Gibson M, Greene J, Ledbetter J . Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science. 1992; 257(5071):792-5. DOI: 10.1126/science.1496399. View

Freeman G, Gribben J, Boussiotis V, Ng J, Restivo Jr V, Lombard L . Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science. 1993; 262(5135):909-11. DOI: 10.1126/science.7694363. View

Thompson C, LINDSTEN T, Ledbetter J, Kunkel S, Young H, Emerson S . CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci U S A. 1989; 86(4):1333-7. PMC: 286684. DOI: 10.1073/pnas.86.4.1333. View

Vincenti F, Charpentier B, Vanrenterghem Y, Rostaing L, Bresnahan B, Darji P . A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 2010; 10(3):535-46. DOI: 10.1111/j.1600-6143.2009.03005.x. View

Hedrick S, Cohen D, Nielsen E, Davis M . Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984; 308(5955):149-53. DOI: 10.1038/308149a0. View

Weber J . Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist. 2007; 12(7):864-72. DOI: 10.1634/theoncologist.12-7-864. View

Finck B, Linsley P, Wofsy D . Treatment of murine lupus with CTLA4Ig. Science. 1994; 265(5176):1225-7. DOI: 10.1126/science.7520604. View

Verwilghen J, Lovis R, de Boer M, Linsley P, Haines G, Koch A . Expression of functional B7 and CTLA4 on rheumatoid synovial T cells. J Immunol. 1994; 153(3):1378-85. View

Poirier N, Chevalier M, Mary C, Hervouet J, Minault D, Baker P . Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates. J Immunol. 2015; 196(1):274-83. DOI: 10.4049/jimmunol.1501810. View

10.

Sandborn W, Colombel J, Sands B, Rutgeerts P, Targan S, Panaccione R . Abatacept for Crohn's disease and ulcerative colitis. Gastroenterology. 2012; 143(1):62-69.e4. DOI: 10.1053/j.gastro.2012.04.010. View

11.

Abrams J, Lebwohl M, Guzzo C, Jegasothy B, Goldfarb M, GOFFE B . CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest. 1999; 103(9):1243-52. PMC: 408469. DOI: 10.1172/JCI5857. View

12.

Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L . Belatacept and Long-Term Outcomes in Kidney Transplantation. N Engl J Med. 2016; 374(4):333-43. DOI: 10.1056/NEJMoa1506027. View

13.

Waterhouse P, Penninger J, Timms E, Wakeham A, Shahinian A, Lee K . Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995; 270(5238):985-8. DOI: 10.1126/science.270.5238.985. View

14.

Linsley P, Clark E, Ledbetter J . T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1. Proc Natl Acad Sci U S A. 1990; 87(13):5031-5. PMC: 54255. DOI: 10.1073/pnas.87.13.5031. View

15.

Kremer J, Dougados M, Emery P, Durez P, Sibilia J, Shergy W . Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase iib, double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005; 52(8):2263-71. DOI: 10.1002/art.21201. View

16.

Abrams J, Kelley S, Hayes E, Kikuchi T, Brown M, Kang S . Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells. J Exp Med. 2000; 192(5):681-94. PMC: 2193278. DOI: 10.1084/jem.192.5.681. View

17.

LINDSTEN T, Lee K, Harris E, Petryniak B, Craighead N, Reynolds P . Characterization of CTLA-4 structure and expression on human T cells. J Immunol. 1993; 151(7):3489-99. View

18.

Suntharalingam G, Perry M, Ward S, Brett S, Castello-Cortes A, Brunner M . Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006; 355(10):1018-28. DOI: 10.1056/NEJMoa063842. View

19.

Webb L, Walmsley M, Feldmann M . Prevention and amelioration of collagen-induced arthritis by blockade of the CD28 co-stimulatory pathway: requirement for both B7-1 and B7-2. Eur J Immunol. 1996; 26(10):2320-8. DOI: 10.1002/eji.1830261008. View

20.

Zhang R, Huynh A, Whitcher G, Chang J, Maltzman J, Turka L . An obligate cell-intrinsic function for CD28 in Tregs. J Clin Invest. 2013; 123(2):580-93. PMC: 3561819. DOI: 10.1172/JCI65013. View