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Immunologic ‘ignorance’ of vascularized organ transplants in the absence of secondary lymphoid tissue

Nature Medicine volume 6, pages 686–688 (2000)Cite this article

Abstract

Secondary lymphoid organs (the spleen, lymph nodes and mucosal lymphoid tissues) provide the proper environment for antigen-presenting cells to interact with and activate naive T and B lymphocytes1. Although it is generally accepted that secondary lymphoid organs are essential for initiating immune responses to microbial antigens and to skin allografts2,3,4,5,6, the prevailing view has been that the immune response to primarily vascularized organ transplants such as hearts and kidneys does not require the presence of secondary lymphoid tissue. The assumption has been that the immune response to such organs is initiated in the graft itself when recipient lymphocytes encounter foreign histocompatibility antigens presented by the graft's endothelial cells7,8,9,10,11,12,13. In contrast to this view, we show here that cardiac allografts are accepted indefinitely in recipient mice that lack secondary lymphoid tissue, indicating that the alloimmune response to a vascularized organ transplant cannot be initiated in the graft itself. Moreover, we demonstrate that the permanent acceptance of these grafts is not due to tolerance but is because of immunologic ‘ignorance’.

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Figure 1: Secondary lymphoid organs are essential for the rejection of vascularized cardiac allografts.
Figure 2: Lymph nodes, but not the spleen, are essential for the rejection of skin allografts.
Figure 3: Cardiac allograft rejection after adoptive transfer of T lymphocytes.

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Acknowledgements

We thank F.K. Baddoura for the histopathologic analyses and C.P. Larsen, R. Ahmed, D. Briscoe and J. S. Pober for discussions. This work was supported by National Institutes of Health grants AI41643 (F.G.L.) and AI44644 (F.G.L.), and by the Carlos and Marguerite Mason Foundation.

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  1. Renal Division, Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, 1670 Clairmont Road, Atlanta, 30033, Georgia, USA

    Fadi G. Lakkis, Alexandr Arakelov, Bogumila T. Konieczny & Yoshihiko Inoue

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  1. Fadi G. Lakkis
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  2. Alexandr Arakelov
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  3. Bogumila T. Konieczny
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Correspondence to Fadi G. Lakkis.

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Lakkis, F., Arakelov, A., Konieczny, B. et al. Immunologic ‘ignorance’ of vascularized organ transplants in the absence of secondary lymphoid tissue. Nat Med 6, 686–688 (2000). https://doi.org/10.1038/76267

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