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The axis of interleukin 12 and gamma interferon regulates acute vascular xenogeneic rejection

Nature Medicine volume 6, pages 549–555 (2000)Cite this article

Abstract

Recent advances using transgenic animals or exogenous complement inhibitors have demonstrated prevention of hyperacute rejection of vascularized organs, but not graft loss due to acute vascular rejection. Using various wild-type and cytokine-deficient mice strains, we have examined the mechanisms of acute vascular rejection. C57BL/6 mice deficient in interleukin12 or gamma interferon showed faster acute vascular rejection than did wild-type mice. Furthermore, mice defective in B-cell development showed no acute vascular rejection. These results demonstrate that the axis of interleukin 12 and gamma interferon provides a survival advantage in vascularized xenografts by delaying or preventing acute vascular rejection caused by a B cell-dependent mechanism.

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Figure 1: Pathology of heart xenografts in BALB/c and C57BL/6 recipient mice.
Figure 2: IFN-γ is expressed more abundantly in C57BL/6 than BALB/c mice.
Figure 3: Pathology of heart xenografts in C57BL/6 IFN-γ−/− and IL-12p40−/− mice.
Figure 4: IFN-γ expression is decreased in C57BL/6 IL-12p40−/− mice.
Figure 5: B cells are required for acute vascular rejection.

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Acknowledgements

The authors appreciate the technical assistance of A. Leaist, D.A. Martin and J.D. Andrews. The authors also thank J. Wang and J. Jiang for their assistance with microsurgeries and A. Jevnikar and B. Singh for their review of this manuscript. This work has been supported by grants from the Multi-Organ Transplant Program of the London Health Sciences Centre, the Kidney Foundation of Canada, and the Heart and Stroke foundation of Canada. D.J.K. is a Medical Research Council of Canada scholar and M.D. is a Medical Research Council of Canada student scholar.

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Author notes

  1. Hao Wang and Mark E. DeVries: H.W. and M.E.D. contributed equally to this study.

Authors and Affiliations

  1. The Experimental Transplantation Surgical Laboratory, John P. Robarts Research Institute, 1400 Western Road, London, N6G 2V4, Ontario, Canada

    Hao Wang, Shaoping Deng & Robert Zhong

  2. The Multi-Organ Transplant Program, London Health Science Centre, 339 Windemere Road, London, N6A 5A5, Ontario, Canada

    Hao Wang, Mark E. DeVries, Shaoping Deng, Masud H. Khandaker, David J. Kelvin & Robert Zhong

  3. Department of Pathology, University of Western Ontario, London, N6A 5C1 , Ontario, Canada

    Hao Wang, Bertha Garcia & Robert Zhong

  4. Department of Medicine, University of Western Ontario, London, N6A 5C1 , Ontario, Canada

    Mark E. DeVries, Masud H. Khandaker, J. Geoff Pickering & Larry H. Chow

  5. Laboratory of Molecular Immunology and Inflammation, John P. Robarts Research Institute, 1400 Western Rd, London, N6G 2V4, Ontario, Canada

    David J. Kelvin

  6. Department of Microbiology and Immunology, University of Western Ontario, London, N6A 5C1, Ontario, Canada

    Mark E. DeVries & Masud H. Khandaker

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  1. Hao Wang
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Correspondence to David J. Kelvin or Robert Zhong.

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Wang, H., DeVries, M., Deng, S. et al. The axis of interleukin 12 and gamma interferon regulates acute vascular xenogeneic rejection. Nat Med 6, 549–555 (2000). https://doi.org/10.1038/75029

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