Targeting Memory T Cells in Type 1 Diabetes
Open accessAbstract
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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β-cell-specific CD8 T cell responses have notable longevity, as shown by T cell-mediated destruction of islet transplantations in patients with longstanding T1D.
“β-cell-specific CD8 T cell responses have notable longevity, which has been shown by the T cell-mediated destruction of islet transplantations in patients with longstanding T1D23.”
From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [23]
The Immunopathology of T1D section describes long-lived autoreactive memory T cells, beta-cell destruction in failed grafts, and antigen-specific CD8+ and CD4+ T cells identified after transplantation. It does not specify that the transplant recipients had longstanding T1D, and it presents the T-cell findings as strong evidence of recurrent autoimmunity rather than direct proof that CD8+ cells alone destroyed the grafts. Page numbers are unavailable in our copy. (LLM, conf=0.84)
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Type 1 diabetes immunotherapy using polyclonal regulatory T cells
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Pathophysiology of Type 1 Diabetes and Gut Microbiota Role
CHIERICO, F. D., Rapini, N., Deodati, A., Matteoli, M. C., Cianfarani, S., & Putignani, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314650 · Cited by 123 · see citing works
Update on Dendritic Cell-Induced Immunological and Clinical Tolerance
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Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial
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Soluble CD137 Ameliorates Acute Type 1 Diabetes by Inducing T Cell Anergy
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Strategies for clinical trials in type 1 diabetes
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Self-citationTargeting Type 1 Diabetes: Selective Approaches for New Therapies
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Stem Cell Educator therapy in type 1 diabetes: From the bench to clinical trials
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Deng, W.-Y., Zhao, Z., Zou, T., Kuang, T.-D., & Wang, J. (2024) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s421527 · Cited by 19 · see citing works
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Mbaye, E. H. A., Scott, E. A., & Burke, J. A. (2025) · Frontiers in Transplantation · doi:10.3389/frtra.2025.1514956 · Cited by 8 · see citing works
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Immune Mechanisms and Translational Therapeutic Challenges in Type 1 Diabetes
Xu, H., Ma, M., Jia, Z., Cuan, S., & Zhang, Y. (2026) · Diabetes Obesity and Metabolism · doi:10.1111/dom.71409
- Authors
- Ehlers, M. R., & Rigby, M. R.
- Affiliations
- Immune Tolerance Network (US)
- Janssen Research & Development (United States) (US)
- Corresponding author
- Ehlers, Mario R.
- ORCID
- Rigby, Mark R.
- Venue
- Current Diabetes Reports
- Published
- 2015-09-14
- Volume
- 15
- Issue
- 11
- Pages
- 84-84
- ISSN
- 1534-4827 (ISSN-L)
- 1539-0829
- PMC
- PMC12373485
- OpenAlex
- W2177631887
- Cited by
- 40
- References
- 89
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 2
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Diabetes Reports (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (UM1AI109565)
- Janssen Research and Development
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, memory T cells, autoreactive T cells, beta cell destruction, CD4+ T cells, CD8+ T cells, regulatory T cells, islet transplantation, beta-cell preservation, T cell depletion, homeostatic cytokines, T cell hyporesponsiveness, immune tolerance
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Homeostasis, Humans, Immunologic Memory, T-Lymphocytes, Signal Transduction, Cytokines
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