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- Title
Expansion of Human Regulatory T-Cells From Patients With Type 1 Diabetes.
- Authors
Putnam, Amy L.; Brusko, Todd M.; Lee, Michael R.; Liu, Weihong; Szot, Gregory L.; Ghosh, Taumoha; Atkinson, Mark A.; Bluestone, Jeffrey A.
- Abstract
OBJECTIVE--Regulatory T-cells (Tregs) have catalyzed the field of immune regulation. However, translating Treg-based therapies from animal models of autoimmunity to human clinical trials requires robust methods for the isolation and expansion of these cells--a need forming the basis for these studies. RESEARCH DESIGN AND METHODS--Tregs from recent-onset type 1 diabetic patients and healthy control subjects were isolated by fluorescence-activated cell sorting and compared for their capacity to expand in vitro in response to anti-CD3-anti-CD28-coated microbeads and IL-2. Expanded cells were examined for suppressive function, lineage markers and FOXP3, and cytokine production. RESULTS--Both CD4+CD127lo/- and CD4+CD127lo/-CD25+ T-cells could be expanded and used as Tregs. However, expansion of CD4+CD127lo/- cells required the addition of rapamycin to maintain lineage purity. In contrast, expansion of CD4+CD127lo/-CD25+ T-cells, especially the CD45RA+ subset, resulted in high yield, functional Tregs that maintained higher FOXP3 expression in the absence of rapamycin. Tregs from type 1 diabetic patients and control subjects expanded similarly and were equally capable of suppressing T-cell proliferation. Regulatory cytokines were produced by Tregs after culture; however, a portion of FOXP3[sup +] cells were capable of producing interferon (IFN)-γ after reactivation. IFN-γ production was observed from both CD45RO+ and CD45RA+ Treg populations. CONCLUSIONS--The results support the feasibility of isolating Tregs for in vitro expansion. Based on expansion capacity, FOXP3 stability, and functional properties, the CD4+CD127lo/- CD25+ T-cells represent a viable cell population for cellular therapy in this autoimmune disease. Diabetes 58:652-662, 2009
- Subjects
T cells; IMMUNOREGULATION; PEOPLE with diabetes; AUTOIMMUNITY; CELLULAR therapy; AUTOIMMUNE diseases
- Publication
Diabetes, 2009, Vol 58, Issue 3, p652
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db08-1168