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Targeting Memory T Cells in Type 1 Diabetes

  • Treatment of Type 1 Diabetes (M Pietropaolo, Section Editor)
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Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease that leads to progressive destruction of pancreatic beta cells. Compared to healthy controls, a characteristic feature of patients with T1D is the presence of self-reactive T cells with a memory phenotype. These autoreactive memory T cells in both the CD4+ and CD8+ compartments are likely to be long-lived, strongly responsive to antigenic stimulation with less dependence on costimulation for activation and clonal expansion, and comparatively resistant to suppression by regulatory T cells (Tregs) or downregulation by immune-modulating agents. Persistence of autoreactive memory T cells likely contributes to the difficulty in preventing disease progression in new-onset T1D and maintaining allogeneic islet transplants by regular immunosuppressive regimens. The majority of immune interventions that have demonstrated some success in preserving beta cell function in the new-onset period have been shown to deplete or modulate memory T cells. Based on these and other considerations, preservation of residual beta cells early after diagnosis or restoration of beta cell mass by use of stem cell or transplantation technology will require a successful strategy to control the autoreactive memory T cell compartment, which could include depletion, inhibition of homeostatic cytokines, induction of hyporesponsiveness, or a combination of these approaches.

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Acknowledgments

This publication was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Number UM1AI109565. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Mario Ehlers declares that he has no conflict of interest. Mark Rigby is an employee of Janssen R&D, Pharmaceutical Companies of Johnson & Johnson.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Clinical Trials Group, Immune Tolerance Network, 185 Berry Street, Suite 3515, San Francisco, CA, 94107, USA

    Mario R. Ehlers

  2. Translational Medicine, Immunology Development, Janssen R&D, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA, 19477, USA

    Mark R. Rigby

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  1. Mario R. Ehlers
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Correspondence to Mario R. Ehlers.

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This article is part of the Topical Collection on Treatment of Type 1 Diabetes

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Ehlers, M.R., Rigby, M.R. Targeting Memory T Cells in Type 1 Diabetes. Curr Diab Rep 15, 84 (2015). https://doi.org/10.1007/s11892-015-0659-5

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