Targeting Homeostatic T Cell Proliferation to Control Beta-Cell Autoimmunity

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Targeting Homeostatic T Cell Proliferation to Control Beta-Cell Autoimmunity

Immunomodulation of the autoreactive T cell response is considered a major strategy to control beta-cell autoimmunity, both in the natural history of type 1 diabetes and in islet transplantation, which can be affected by autoimmunity recurrence. So far, these strategies have had modest results, prompting efforts to define novel cellular and molecular targets to control autoreactive T cell expan...

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Development of tumor immunotherapies focuses on inducing autoimmune responses against tumor-associated self-antigens primarily encoded by normal, unmutated genes. We hypothesized that such responses could be elicited by T cell homeostatic proliferation in the periphery, involving expansion of T cells recognizing self-MHC/peptide ligands. Herein, we demonstrate that sublethally irradiated lympho...

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Homeostatic T Cell Proliferation

Through positive and negative selection, the thymus allows a small fraction of immature CD4 ϩ 8 ϩ double positive thymocytes to differentiate into mature CD4 ϩ 8 Ϫ or CD4 Ϫ 8 ϩ single positive cells; these cells are released into the periphery to establish the mature T cell pool. Positive selection rescues thymocytes that express TCR with low affinity for peptides bound to MHC molecules express...

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Homeostatic T Cell Proliferation after Islet Transplantation

Pancreatic islet transplantation in patients with type 1 diabetes mellitus is performed under immunosuppression to avoid alloreactive T cell responses and to control the reactivation of autoreactive memory T cells. However, lymphopenia associated with immunosuppression and T cell depletion can induce a paradoxical expansion of lymphocyte subsets under the influence of homeostatic proliferation....

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Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation.

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ژورنال

عنوان ژورنال: Current Diabetes Reports

سال: 2016

ISSN: 1534-4827,1539-0829

DOI: 10.1007/s11892-016-0731-9