The Effects of Tolerance on Allograft Damage Caused by the Innate Immune System

Overview

Journal Transplantation

Specialty General Surgery

Date 2008 Feb 28

PMID 18301326

Citations 2

Authors

Ruediger Hoerbelt

Christopher L Benjamin

Tsuyoshi Shoji

Stuart L Houser

Ashok Muniappan

Rebecca S Hasse

Levi G Ledgerwood

James S Allan

David H Sachs

Joren C Madsen

Affiliations

Soon will be listed here.

Abstract

Background: It is not known whether tolerance can be induced in a strong proinflammatory milieu or whether the induction of tolerance can prevent interferon (IFN)-gamma-associated graft injury. To address these questions, we studied the effects of rIFN-gamma infusion on porcine cardiac allograft survival.

Methods: Recombinant interferon (rIFN)-gamma was continuously infused into the left anterior descending artery of hearts transplanted into major histocompatibility complex-inbred miniature swine treated with a 12-day course of cyclosporine A. Group 1 recipients received a nearly syngeneic heart, group 2 recipients received a class I disparate heart, and group 3 recipients were cotransplanted with a class I-disparate heart and kidney, a procedure demonstrated to induce tolerance to both grafts. A fourth group of animals were not transplanted but received intracoronary rIFN-gamma infusion into the native heart.

Results: rIFN-gamma perfusion not only accelerated the acute rejection of class I-disparate hearts (mean survival time, 19+/-7.21 vs. 38+/-8.19; P=0.025) but caused near-syngeneic heart transplants, which otherwise survived indefinitely, to reject within 35 days. In contrast, rIFN-gamma perfusion had no demonstrable effects on hearts grafts in tolerant recipients or on autologous hearts.

Conclusions: These results suggest that tolerance induction can occur in the presence of IFN-gamma-mediated inflammation, and that tolerance induction can prevent the tissue injury caused by the overproduction of IFN-gamma. This suggests that the beneficial effects of tolerance may include protection from nonspecific inflammatory responses, such as those produced by ischemia-reperfusion injury and brain death.

Citing Articles

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References

Terasaki P, Cecka J, Gjertson D, Takemoto S . High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med. 1995; 333(6):333-6. DOI: 10.1056/NEJM199508103330601. View

Mezrich J, Yamada K, Lee R, Mawulawde K, Benjamin L, Schwarze M . Induction of tolerance to heart transplants by simultaneous cotransplantation of donor kidneys may depend on a radiation-sensitive renal-cell population. Transplantation. 2003; 76(4):625-31. DOI: 10.1097/01.TP.0000079926.80833.42. View

Nagano H, Libby P, Taylor M, Hasegawa S, Stinn J, Becker G . Coronary arteriosclerosis after T-cell-mediated injury in transplanted mouse hearts: role of interferon-gamma. Am J Pathol. 1998; 152(5):1187-97. PMC: 1858591. View

Ring G, Saleem S, Dai Z, Hassan A, Konieczny B, Baddoura F . Interferon-gamma is necessary for initiating the acute rejection of major histocompatibility complex class II-disparate skin allografts. Transplantation. 1999; 67(10):1362-5. DOI: 10.1097/00007890-199905270-00012. View

Takada M, Nadeau K, Hancock W, Mackenzie H, Shaw G, Waaga A . Effects of explosive brain death on cytokine activation of peripheral organs in the rat. Transplantation. 1998; 65(12):1533-42. DOI: 10.1097/00007890-199806270-00001. View

Howard T, Klintmalm G, Cofer J, Husberg B, Goldstein R, Gonwa T . The influence of preservation injury on rejection in the hepatic transplant recipient. Transplantation. 1990; 49(1):103-7. DOI: 10.1097/00007890-199001000-00023. View

Willems F, Marchant A, Delville J, Gerard C, Delvaux A, Velu T . Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes. Eur J Immunol. 1994; 24(4):1007-9. DOI: 10.1002/eji.1830240435. View

Panitch H, Hirsch R, Haley A, Johnson K . Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet. 1987; 1(8538):893-5. DOI: 10.1016/s0140-6736(87)92863-7. View

Goes N, Urmson J, Hobart M, Halloran P . The unique role of interferon-gamma in the regulation of MHC expression on arterial endothelium. Transplantation. 1996; 62(12):1889-94. DOI: 10.1097/00007890-199612270-00036. View

10.

Zhao D, Hu Y, Miller G, Luster A, Mitchell R, Libby P . Differential expression of the IFN-gamma-inducible CXCR3-binding chemokines, IFN-inducible protein 10, monokine induced by IFN, and IFN-inducible T cell alpha chemoattractant in human cardiac allografts: association with cardiac allograft.... J Immunol. 2002; 169(3):1556-60. DOI: 10.4049/jimmunol.169.3.1556. View

11.

Daemen M, Vant Veer C, Wolfs T, Buurman W . Ischemia/reperfusion-induced IFN-gamma up-regulation: involvement of IL-12 and IL-18. J Immunol. 1999; 162(9):5506-10. View

12.

Lee R, Yamada K, Houser S, Womer K, Maloney M, Rose H . Indirect recognition of allopeptides promotes the development of cardiac allograft vasculopathy. Proc Natl Acad Sci U S A. 2001; 98(6):3276-81. PMC: 30644. DOI: 10.1073/pnas.051584498. View

13.

Hassan A, Dai Z, Konieczny B, Ring G, Baddoura F, El-Sayed A . Regulation of alloantigen-mediated T-cell proliferation by endogenous interferon-gamma: implications for long-term allograft acceptance. Transplantation. 1999; 68(1):124-9. DOI: 10.1097/00007890-199907150-00023. View

14.

Groenewegen G, Buurman W, van der Linden C . Lymphokine dependence of in vivo expression of MHC class II antigens by endothelium. Nature. 1985; 316(6026):361-3. DOI: 10.1038/316361a0. View

15.

Madsen J, Yamada K, Allan J, Choo J, Erhorn A, Pins M . Transplantation tolerance prevents cardiac allograft vasculopathy in major histocompatibility complex class I-disparate miniature swine. Transplantation. 1998; 65(3):304-13. DOI: 10.1097/00007890-199802150-00002. View

16.

Yamada K, Mawulawde K, Menard M, Shimizu A, Aretz H, Choo J . Mechanisms of tolerance induction and prevention of cardiac allograft vasculopathy in miniature swine: the effect of augmentation of donor antigen load. J Thorac Cardiovasc Surg. 2000; 119(4 Pt 1):709-19. DOI: 10.1016/S0022-5223(00)70005-5. View

17.

Goes N, Sims T, Urmson J, Vincent D, Ramassar V, Halloran P . Disturbed MHC regulation in the IFN-gamma knockout mouse. Evidence for three states of MHC expression with distinct roles for IFN-gamma. J Immunol. 1995; 155(10):4559-66. View

18.

Akyurek L, Johnsson C, Lange D, Georgii-Hemming P, Larsson E, Fellstrom B . Tolerance induction ameliorates allograft vasculopathy in rat aortic transplants. Influence of Fas-mediated apoptosis. J Clin Invest. 1998; 101(12):2889-99. PMC: 508881. DOI: 10.1172/JCI1177. View

19.

Pennington L, Lunney J, Sachs D . Transplantation in miniature swine. VIII. Recombination within the major histocompatibility complex of miniature swine. Transplantation. 1981; 31(1):66-71. View

20.

Tellides G, Tereb D, Kirkiles-Smith N, Kim R, Wilson J, Schechner J . Interferon-gamma elicits arteriosclerosis in the absence of leukocytes. Nature. 2000; 403(6766):207-11. DOI: 10.1038/35003221. View