Changes in T-cell subsets identify responders to FcR-nonbinding anti-CD3 mAb (teplizumab) in patients with type 1 diabetes.

Autor: Tooley JE; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.; Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA., Vudattu N; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.; Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA., Choi J; Department of Neurology, Yale School of Medicine, New Haven, CT, USA., Cotsapas C; Department of Neurology, Yale School of Medicine, New Haven, CT, USA., Devine L; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA., Raddassi K; Department of Neurology, Yale School of Medicine, New Haven, CT, USA., Ehlers MR; Immune Tolerance Network, Bethesda, MD, USA., McNamara JG; National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA., Harris KM; Immune Tolerance Network, Bethesda, MD, USA., Kanaparthi S; Immune Tolerance Network, Bethesda, MD, USA., Phippard D; Immune Tolerance Network, Bethesda, MD, USA., Herold KC; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.; Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2016 Jan; Vol. 46 (1), pp. 230-41. Date of Electronic Publication: 2015 Dec 14.
DOI: 10.1002/eji.201545708
Abstrakt: The mechanisms whereby immune therapies affect progression of type 1 diabetes (T1D) are not well understood. Teplizumab, an FcR nonbinding anti-CD3 mAb, has shown efficacy in multiple randomized clinical trials. We previously reported an increase in the frequency of circulating CD8(+) central memory (CD8CM) T cells in clinical responders, but the generalizability of this finding and the molecular effects of teplizumab on these T cells have not been evaluated. We analyzed data from two randomized clinical studies of teplizumab in patients with new- and recent-onset T1D. At the conclusion of therapy, clinical responders showed a significant reduction in circulating CD4(+) effector memory T cells. Afterward, there was an increase in the frequency and absolute number of CD8CM T cells. In vitro, teplizumab expanded CD8CM T cells by proliferation and conversion of non-CM T cells. Nanostring analysis of gene expression of CD8CM T cells from responders and nonresponders versus placebo-treated control subjects identified decreases in expression of genes associated with immune activation and increases in expression of genes associated with T-cell differentiation and regulation. We conclude that CD8CM T cells with decreased activation and regulatory gene expression are associated with clinical responses to teplizumab in patients with T1D.
(© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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