Reduced Follicular Regulatory T Cells in Spleen and Pancreatic Lymph Nodes of Patients With Type 1 Diabetes.

Autor:	Vecchione A; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY., Jofra T; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Gerosa J; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Shankwitz K; Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Di Fonte R; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Galvani G; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Ippolito E; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Cicalese MP; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Vita-Salute San Raffaele University, Milan, Italy., Schultz AR; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL., Seay HR; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL., Favellato M; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Milardi G; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Stabilini A; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Ragogna F; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Grogan P; Department of Internal Medicine, IRCCS San Raffaele Hospital, Milan, Italy.; TrialNet Clinical Center, IRCCS San Raffaele Hospital, Milan, Italy., Bianconi E; Department of Internal Medicine, IRCCS San Raffaele Hospital, Milan, Italy.; TrialNet Clinical Center, IRCCS San Raffaele Hospital, Milan, Italy., Laurenzi A; Department of Internal Medicine, IRCCS San Raffaele Hospital, Milan, Italy., Caretto A; Department of Internal Medicine, IRCCS San Raffaele Hospital, Milan, Italy., Nano R; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Melzi R; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Danzl N; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY., Bosi E; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Vita-Salute San Raffaele University, Milan, Italy.; Department of Internal Medicine, IRCCS San Raffaele Hospital, Milan, Italy.; TrialNet Clinical Center, IRCCS San Raffaele Hospital, Milan, Italy., Piemonti L; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Vita-Salute San Raffaele University, Milan, Italy.; Department of Internal Medicine, IRCCS San Raffaele Hospital, Milan, Italy., Aiuti A; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Vita-Salute San Raffaele University, Milan, Italy., Brusko T; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL.; Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL., Petrovas C; Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Battaglia M; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.; TrialNet Clinical Center, IRCCS San Raffaele Hospital, Milan, Italy., Fousteri G; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy fousteri.georgia@hsr.it.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2021 Dec; Vol. 70 (12), pp. 2892-2902. Date of Electronic Publication: 2021 Oct 07.
DOI:	10.2337/db21-0091
Abstrakt:	In the attempt to understand the origin of autoantibody (AAb) production in patients with and at risk for type 1 diabetes (T1D), multiple studies have analyzed and reported alterations in T follicular helper (Tfh) cells in presymptomatic AAb + subjects and patients with T1D. Yet, whether the regulatory counterpart of Tfh cells, represented by T follicular regulatory (Tfr) cells, is similarly altered is still unclear. To address this question, we performed analyses in peripheral blood, spleen, and pancreatic lymph nodes (PLN) of organ donor subjects with T1D. Blood analyses were also performed in living AAb - and AAb + subjects. While negligible differences in the frequency and phenotype of blood Tfr cells were observed among T1D, AAb - , and AAb + adult subjects, the frequency of Tfr cells was significantly reduced in spleen and PLN of T1D as compared with nondiabetic control subjects. Furthermore, adoptive transfer of Tfr cells delayed disease development in a mouse model of T1D, a finding that could indicate that Tfr cells play an important role in peripheral tolerance and regulation of autoreactive Tfh cells. Together, our findings provide evidence of Tfr cell alterations within disease-relevant tissues in patients with T1D, suggesting a role for Tfr cells in defective humoral tolerance and disease pathogenesis. (© 2021 by the American Diabetes Association.)
Databáze:	MEDLINE
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