1. Reduced Follicular Regulatory T Cells in Spleen and Pancreatic Lymph Nodes of Patients With Type 1 Diabetes
- Author
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Andrea Vecchione, Maria Pia Cicalese, Mariagrazia Favellato, Raffaela Melzi, Constantinos Petrovas, Elio Ippolito, Giuseppe Galvani, Kimberly Shankwitz, Eleonora Bianconi, Alessandro Aiuti, Angela Stabilini, Nichole Danzl, Manuela Battaglia, Roberta Di Fonte, Lorenzo Piemonti, Georgia Fousteri, Francesca Ragogna, Pauline Grogan, Emanuele Bosi, Rita Nano, Andrea Laurenzi, Todd M. Brusko, Jolanda Gerosa, Giulia Milardi, Tatiana Jofra, Howie R Seay, Amelia Caretto, Andrew R Schultz, Vecchione, Andrea, Jofra, Tatiana, Gerosa, Jolanda, Shankwitz, Kimberly, Di Fonte, Roberta, Galvani, Giuseppe, Ippolito, Elio, Cicalese, Maria Pia, Schultz, Andrew R, Seay, Howie R, Favellato, Mariagrazia, Milardi, Giulia, Stabilini, Angela, Ragogna, Francesca, Grogan, Pauline, Bianconi, Eleonora, Laurenzi, Andrea, Caretto, Amelia, Nano, Rita, Melzi, Raffaela, Danzl, Nichole, Bosi, Emanuele, Piemonti, Lorenzo, Aiuti, Alessandro, Brusko, Todd, Petrovas, Constantino, Battaglia, Manuela, and Fousteri, Georgia
- Subjects
Adult ,Adoptive cell transfer ,endocrine system ,Endocrinology, Diabetes and Metabolism ,Cell ,Spleen ,Mice, SCID ,T-Lymphocytes, Regulatory ,Pancreatic Lymph Node ,Mice ,Mice, Inbred NOD ,Follicular phase ,Internal Medicine ,medicine ,Animals ,Humans ,Lymphocyte Count ,Pancreas ,Cells, Cultured ,Type 1 diabetes ,business.industry ,Autoantibody ,Peripheral tolerance ,medicine.disease ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Diabetes Mellitus, Type 1 ,Case-Control Studies ,Immunology ,Lymph Nodes ,Immunology and Transplantation ,business - Abstract
In the attempt to understand the origin of autoantibody (AAb) production in patients with and at-risk for T1D, multiple studies have analyzed and reported alterations in follicular helper T cells (Tfh) in presymptomatic AAb-positive subjects and patients with T1D. Yet, it is still not clear whether the regulatory counterpart of Tfh cells, represented by follicular regulatory T cells (Tfr), is similarly altered. 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-negative and -positive subjects. While negligible differences in the frequency and phenotype of blood Tfr cells were observed between T1D, AAb-negative and AAb-positive adult subjects, the frequency of Tfr cells was significantly reduced in spleen and PLN of T1D as compared to non-diabetic controls. 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.
- Published
- 2021