CD28 Ligation Induces Transplantation Tolerance by IFN-gamma-dependent Depletion of T Cells That Recognize Alloantigens

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2004 Jun 3

PMID 15173889

Citations 25

Authors

Xue-Zhong Yu

Michael H Albert

Paul J Martin

Claudio Anasetti

Affiliations

Soon will be listed here.

Abstract

Administration of an agonistic anti-CD28 mAb paradoxically inhibits donor T cell expansion and prevents graft-versus-host disease (GVHD) in mice. Here we examined the mechanism of anti-CD28-mediated immunosuppression and found that anti-CD28 mAb activated, rather than blocked, CD28-mediated signaling in vivo. Anti-CD28 treatment prevented GVHD by selectively depleting alloantigen-activated donor T cells through apoptosis but spared the T cells that did not recognize recipient alloantigens. Overexpression of Bcl-x(L) did not protect T cells from depletion and did not affect GVHD prevention after anti-CD28 treatment. Depletion of activated T cells mediated through CD28 did not depend on the expression of death receptors Fas and TNF receptors type I and II, but both the depletion of activated T cells and the suppressive effect of anti-CD28 mAb on GVHD lethality required donor-derived IFN-gamma production. This study demonstrates that agonistic Ab's specific for the CD28 costimulatory molecule may be used as novel therapeutic agents to abrogate pathogenic T cell responses by selective depletion of activated T cells.

Citing Articles

Therapeutic role of interferon-γ in experimental autoimmune encephalomyelitis is mediated through a tolerogenic subset of splenic CD11b myeloid cells.

Arellano G, Acuna E, Loda E, Moore L, Tichauer J, Castillo C J Neuroinflammation. 2024; 21(1):144.

PMID: 38822334 PMC: 11143617. DOI: 10.1186/s12974-024-03126-3.

CD28 blockade controls T cell activation to prevent graft-versus-host disease in primates.

Watkins B, Tkachev V, Furlan S, Hunt D, Betz K, Yu A J Clin Invest. 2018; 128(9):3991-4007.

PMID: 30102255 PMC: 6118599. DOI: 10.1172/JCI98793.

Advance in Targeted Immunotherapy for Graft-Versus-Host Disease.

Zhang L, Yu J, Wei W Front Immunol. 2018; 9:1087.

PMID: 29868032 PMC: 5964137. DOI: 10.3389/fimmu.2018.01087.

CD28 Costimulation of T Helper 1 Cells Enhances Cytokine Release .

Langenhorst D, Haack S, Gob S, Uri A, Luhder F, Vanhove B Front Immunol. 2018; 9:1060.

PMID: 29868020 PMC: 5964139. DOI: 10.3389/fimmu.2018.01060.

Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co-stimulation on Donor CD4 Foxp3 Regulatory T Cells.

Uri A, Werner S, Luhder F, Hunig T, Kerkau T, Beyersdorf N Front Immunol. 2017; 8:721.

PMID: 28690612 PMC: 5481316. DOI: 10.3389/fimmu.2017.00721.

References

Kaneko H, Saito K, Hashimoto H, Yagita H, Okumura K, Azuma M . Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis. Clin Exp Immunol. 1996; 106(2):218-29. PMC: 2200594. DOI: 10.1046/j.1365-2249.1996.d01-849.x. View

Yu X, Martin P, Anasetti C . Role of CD28 in acute graft-versus-host disease. Blood. 1998; 92(8):2963-70. View

Van Parijs L, Ibraghimov A, Abbas A . The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity. 1996; 4(3):321-8. DOI: 10.1016/s1074-7613(00)80440-9. View

Kishimoto K, Sandner S, Imitola J, Sho M, Li Y, Langmuir P . Th1 cytokines, programmed cell death, and alloreactive T cell clone size in transplant tolerance. J Clin Invest. 2002; 109(11):1471-9. PMC: 150996. DOI: 10.1172/JCI14947. View

Harding F, McArthur J, Gross J, Raulet D, Allison J . CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992; 356(6370):607-9. DOI: 10.1038/356607a0. View

Yang Y, Dey B, Sergio J, Pearson D, Sykes M . Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12. J Clin Invest. 1998; 102(12):2126-35. PMC: 509167. DOI: 10.1172/JCI4992. View

Iezzi G, Karjalainen K, Lanzavecchia A . The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity. 1998; 8(1):89-95. DOI: 10.1016/s1074-7613(00)80461-6. View

Strasser A, Harris A, Huang D, Krammer P, Cory S . Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J. 1995; 14(24):6136-47. PMC: 394738. DOI: 10.1002/j.1460-2075.1995.tb00304.x. View

Blazar B, Taylor P, Panoskaltsis-Mortari A, Sharpe A, Vallera D . Opposing roles of CD28:B7 and CTLA-4:B7 pathways in regulating in vivo alloresponses in murine recipients of MHC disparate T cells. J Immunol. 1999; 162(11):6368-77. View

10.

Markovic-Plese S, Cortese I, Wandinger K, McFarland H, Martin R . CD4+CD28- costimulation-independent T cells in multiple sclerosis. J Clin Invest. 2001; 108(8):1185-94. PMC: 209525. DOI: 10.1172/JCI12516. View

11.

Dengler T, Szabo G, Sido B, Nottmeyer W, Zimmerman R, Vahl C . Prolonged allograft survival but no tolerance induction by modulating CD28 antibody JJ319 after high-responder rat heart transplantation. Transplantation. 1999; 67(3):392-8. DOI: 10.1097/00007890-199902150-00009. View

12.

Vacchio M, Hodes R . CD28 costimulation is required for in vivo induction of peripheral tolerance in CD8 T cells. J Exp Med. 2003; 197(1):19-26. PMC: 2193800. DOI: 10.1084/jem.20021429. View

13.

Refaeli Y, Van Parijs L, Alexander S, Abbas A . Interferon gamma is required for activation-induced death of T lymphocytes. J Exp Med. 2002; 196(7):999-1005. PMC: 2194022. DOI: 10.1084/jem.20020666. View

14.

Konieczny B, Dai Z, Elwood E, Saleem S, Linsley P, Baddoura F . IFN-gamma is critical for long-term allograft survival induced by blocking the CD28 and CD40 ligand T cell costimulation pathways. J Immunol. 1998; 160(5):2059-64. View

15.

Wells A, Li X, Li Y, Walsh M, Zheng X, Wu Z . Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance. Nat Med. 1999; 5(11):1303-7. DOI: 10.1038/15260. View

16.

Nicolls M, Coulombe M, Yang H, Bolwerk A, Gill R . Anti-LFA-1 therapy induces long-term islet allograft acceptance in the absence of IFN-gamma or IL-4. J Immunol. 2000; 164(7):3627-34. DOI: 10.4049/jimmunol.164.7.3627. View

17.

Rajagopalan G, Smart M, Marietta E, David C . Staphylococcal enterotoxin B-induced activation and concomitant resistance to cell death in CD28-deficient HLA-DQ8 transgenic mice. Int Immunol. 2002; 14(7):801-12. DOI: 10.1093/intimm/dxf047. View

18.

Boise L, Minn A, Noel P, June C, Accavitti M, Lindsten T . CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-xL. Immunity. 1995. 3: 87-98. J Immunol. 2010; 185(7):3788-99. View

19.

Jenkins M, Schwartz R . Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med. 1987; 165(2):302-19. PMC: 2188516. DOI: 10.1084/jem.165.2.302. View

20.

Tan P, Anasetti C, Hansen J, Melrose J, Brunvand M, Bradshaw J . Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med. 1993; 177(1):165-73. PMC: 2190874. DOI: 10.1084/jem.177.1.165. View