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Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28−/− mice

Nature Medicine volume 7, pages 557–562 (2001)Cite this article

Abstract

Successful transplantation of allogeneic organs is an important objective in modern medicine. However, sophisticated immune defense mechanisms, primarily evolved to combat infections, often work against medical transplantation. To investigate the roles of natural and adaptive immune responses in transplant rejection, we functionally inactivated key effector systems of the innate (NK cells) and the adaptive immune system (CD28-mediated costimulation of T cells) in mice. Neither of these interventions alone led to acceptance of allogeneic vascularized cardiac grafts. In contrast, inhibition of NK-receptor–bearing cells combined with CD28-costimulation blockade established long-term graft acceptance. These results indicate a concerted interplay between innate and adaptive immune surveillance for graft rejection. Thus we suggest that inactivation of NK-receptor–bearing cells could be a new strategy for successful survival of solid-organ transplants.

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Figure 1: Allogenic cardiac grafts are rejected in CD28−/−.
Figure 2: Semi-identical grafts are accepted in CD28−/− hosts.
Figure 3: Reduced cytokine transcription in semi-identical grafts in CD28−/− hosts.
Figure 4: Cellular infiltration into grafted hearts.
Figure 5: Depletion of NK-receptor–bearing cells leads to prolonged survival of allogeneic cardiac grafts in CD28−/− recipients.

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Acknowledgements

We thank K. Mink and U. Huffstatt for technical assistance; Y. Chvatcho and M. Kosco-Vilbois for the antibody against NK1.1; R. Endres, N. Zantl, T. Plitz, and H. Neubauer for helpful discussions; N. Zantl for help with microsurgical techniques; and H. Wagner and J.-R. Siewert for continuous and generous support. Grants for these studies was provided by the DFG (259/2-4 to K.P. and Si208/ 5-1/ SFB576 to K.P. and C.-D.H.). This work forms part of an M.D. thesis of C. Tertilt and N. Chambron.

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  1. Stefan Maier and Christine Tertilt: S.M. and C.T. contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Immunology and Hygiene, Technische Universität München, Munich, Germany

    Stefan Maier, Nicole Chambron, Klaus Gerauer, Norbert Hüser & Claus-Dieter Heidecke

  2. Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany

    Christine Tertilt & Klaus Pfeffer

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Correspondence to Klaus Pfeffer.

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Maier, S., Tertilt, C., Chambron, N. et al. Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28−/− mice. Nat Med 7, 557–562 (2001). https://doi.org/10.1038/87880

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