The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Expansion of Human Regulatory T-Cells From Patients With Type 1 Diabetes
Open accessAbstract
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+ 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.
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Cites
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CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
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Self-citationAssociation of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease
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Self-citationCD4+CD25high Regulatory Cells in Human Peripheral Blood
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In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes
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Self-citationType 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies
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Regulation of Immune Responses by mTOR
Powell, J. D., Pollizzi, K. N., Heikamp, E. B., & Horton, M. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075024 · Cited by 836
Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease
DuPage, M., & Bluestone, J. A. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.18 · Cited by 513
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Metadata
- Authors
- Putnam, A. L., Brusko, T. M., Lee, M. R., Liu, W., Szot, G. L., Ghosh, T., Atkinson, M. A., & Bluestone, J. A.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2009-03-01
- Volume
- 58
- Issue
- 3
- Pages
- 652-662
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2137227986
- Cited by
- 357
- References
- 48
- FWCI
- 9.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
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