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Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health

Arif, Sefina, Tree, Timothy I., Astill, Thomas P., Tremble, Jennifer M., Bishop, Amanda J., Dayan, Colin Mark ORCID:, Roep, Bart O. and Peakman, Mark 2004. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. The Journal of Clinical Investigation 113 (3) , pp. 451-463. 10.1172/JCI19585

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According to the quality of response they mediate, autoreactive T cells recognizing islet β cell peptides could represent both disease effectors in the development of type 1 diabetes (T1DM) and directors of tolerance in nondiabetic individuals or those undergoing preventative immunotherapy. A combination of the rarity of these cells, inadequate technology, and poorly defined epitopes, however, has hampered examination of this paradigm. We have identified a panel of naturally processed islet epitopes by direct elution from APCs bearing HLA-DR4. Employing these epitopes in a sensitive, novel cytokine enzyme-linked immunosorbent spot assay, we show that the quality of autoreactive T cells in patients with T1DM exhibits extreme polarization toward a proinflammatory Th1 phenotype. Furthermore, we demonstrate that rather than being unresponsive, the majority of nondiabetic, HLA-matched control subjects also manifest a response against islet peptides, but one that shows extreme T regulatory cell (Treg, IL-10–secreting) bias. We conclude that development of T1DM depends on the balance of autoreactive Th1 and Treg cells, which may be open to favorable manipulation by immune intervention.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Last Modified: 27 Oct 2022 08:52

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