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Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells

Nature volume 398, pages 341–344 (1999)Cite this article

A Corrigendum to this article was published on 21 September 2000

Abstract

Autoantigens found on pancreatic islets can move to draining lymph nodes, where they are able to cause the activation and consequent deletion of autoreactive T cells by a mechanism termed cross-tolerance1,2. This deletion depends on signalling through CD95 (also known as Fas), a member of the superfamily of tumour-necrosis-factor receptors3. Here we describe a new mechanism that protects against autoimmunity: this mechanism involves another member of this superfamily, CD30, whose function was largely unknown. CD30-deficient islet-specific CD8-positive T cells are roughly 6,000-fold more autoaggressive than wild-type cells, with the transfer of as few as 160 CD30-deficient T cells leading to the complete destruction of pancreatic islets and the rapid onset of diabetes. We show that, in the absence of CD30 signalling, cells activated but not yet deleted by the CD95-dependent cross-tolerance mechanism gain the ability to proliferate extensively upon secondary encounter with antigen on parenchymal tissues, such as the pancreatic islets. Thus, CD30 signalling limits the proliferative potential of autoreactive CD8 effector T cells and protects the body against autoimmunity.

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Figure 1: Expansion of CD30-deficient OT-I cells on days 4 and 5 after transfer into RIP-mOVA mice.
Figure 2: CD30 deficiency leads to extensive proliferation of OT-I cells in the islets of RIP-mOVA mice.
Figure 3: The expansion of autoreactive CD8+ T cells requires their interaction withboth bone-marrow-derived APCs and parenchymal tissue cells.

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Acknowledgements

We thank T. Mak for the CD30-deficient mice; J. Allison for advice; and T.Banjanin, F. Karamalis and P. Nathan for technical assistance. C.K. was supported in part by a fellowship from the Deutsche Forschungsgemeinschaft. This work was funded by the NIH, the National Health and Medical Research Council of Australia and the Australian Research Council.

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Authors and Affiliations

  1. The Department of Nephrology, Medizinische Hochschule, 30625, Hannover, Germany

    Christian Kurts & Karl M. Koch

  2. The Department of Pathology and Immunology, Monash Medical School, Prahran, 3181, Victoria, Australia

    Francis R. Carbone

  3. The Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3050, Victoria, Australia

    Matthew F. Krummel, Jacques F. A. P. Miller & William R. Heath

Authors
  1. Christian Kurts
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  2. Francis R. Carbone
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  6. William R. Heath
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Correspondence to Francis R. Carbone or William R. Heath.

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Kurts, C., Carbone, F., Krummel, M. et al. Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells. Nature 398, 341–344 (1999). https://doi.org/10.1038/18692

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