Evaluation of thymic function after autologous hematopoietic stem cell transplanta...
| Full text | |
| Author(s): Show less - |
Malmegrim, Kelen C. R.
;
de Azevedo, Julia T. C.
;
Arruda, Lucas C. M.
;
Abreu, Joana R. F.
;
Couri, Carlos E. B.
;
de Oliveira, Gislane L. V.
;
Palma, Patricia V. B.
;
Scortegagna, Gabriela T.
;
Stracieri, Ana B. P. L.
;
Moraes, Daniela A.
;
Dias, Juliana B. E.
;
Pieroni, Fabiano
;
Cunha, Renato
;
Guilherme, Luiza
;
Santos, Nathalia M.
;
Foss, Milton C.
;
Covas, Dimas T.
;
Burt, Richard K.
;
Simoes, Belinda P.
;
Voltarelli, Julio C.
;
Roep, Bart O.
;
Oliveira, Maria C.
Total Authors: 22
|
| Document type: | Journal article |
| Source: | FRONTIERS IN IMMUNOLOGY; v. 8, FEB 22 2017. |
| Web of Science Citations: | 23 |
| Abstract | |
Autologous hematopoietic stem cell transplantation (AHSCT) increases C-peptide levels and induces insulin independence in patients with type 1 diabetes. This study aimed to investigate how clinical outcomes may associate with the immunological status, especially concerning the balance between immunoregulation and autoreactivity. Twenty-one type 1 diabetes patients were monitored after AHSCT and assessed every 6 months for duration of insulin independence, C-peptide levels, frequencies of islet-specific autoreactive CD8+ T cells (CTL), regulatory lymphocyte subsets, thymic function, and T-cell repertoire diversity. In median follow-up of 78 (range 15-106) months, all patients became insulin-independent, resuming insulin after median of 43 (range 6-100) months. Patients were retrospectively divided into short-or prolonged-remission groups, according to duration of insulin independence. For the entire follow-up, CD3+ CD4+ T-cell numbers remained lower than baseline in both groups, whereas CD3+ CD8+ T-cell levels did not change, resulting in a CD4/CD8 ratio inversion. Memory CTL comprehended most of T cells detected on long-term follow-up of patients after AHSCT. B cells reconstituted to baseline levels at 2-3 months post-AHSCT in both patient groups. In the prolonged-remission-group, baseline islet-specific T-cell autoreactivity persisted after transplantation, but regulatory T cell counts increased. Patients with lower frequencies of autoreactive islet-specific T cells remained insulin-free longer and presented greater C-peptide levels than those with lower frequencies of these cells. Therefore, immune monitoring identified a subgroup of patients with superior clinical outcome of AHSCT. Our study shows that improved immunoregulation may balance autoreactivity endorsing better metabolic outcomes in patients with lower frequencies of islet-specific T cells. Development of new strategies of AHSCT is necessary to increase frequency and function of T and B regulatory cells and decrease efficiently autoreactive islet-specific T and B memory cells in type 1 diabetes patients undergoing transplantation. (AU) | |
| FAPESP's process: | 13/08135-2 - CTC - Center for Cell-Based Therapy |
| Grantee: | Dimas Tadeu Covas |
| Support type: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |