期刊
BLOOD
卷 112, 期 6, 页码 2554-2562出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-04-152041
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资金
- Seed Funding for Basic Research
- University Research Committee
- University of Hong Kong (HKU), Hong Kong SAR, PR China
- Competitive Earmarked Research Grant
- Research Grants Council of Hong Kong, Hong Kong SAR, PR China [HKU 777407M]
- Research Fund for the Control of Infectious Diseases, Hong Kong SAR, PR China [07060482]
- HKU postgraduate studentships
- National Institutes of Health [P01 AI-050153]
CD4(+) CD25(+) Foxp3(+) regulatory T cells (Treg) play an important role in the induction and maintenance of immune tolerance. Although adoptive transfer of bulk populations of Treg can prevent or treat T cell-mediated inflammatory diseases and transplant allograft rejection in animal models, optimal Treg immunotherapy in humans would ideally use antigen-specific rather than polyclonal Treg for greater specificity of regulation and avoidance of general suppression. However, no robust approaches have been reported for the generation of human antigen-specific Treg at a practical scale for clinical use. Here, we report a simple and cost-effective novel method to rapidly induce and expand large numbers of functional human alloantigenspecific Treg from antigenically naive precursors in vitro using allogeneic non-transformed B cells as stimulators. By this approach naive CD4(+) CD25-T cells could be expanded 8-fold into alloantigen-specific Treg after 3 weeks of culture without any exogenous cytokines. The induced alloantigen-specific Treg were CD45RO(+) CCR7-memory cells, and had a CD4(high), CD25(+), Foxp3(+), and CD62L (L-selectin)(+) phenotype. Although these CD4(high)CD25(+) Foxp3(+) alloantigen-specific Treg had no cytotoxic capacity, their suppressive function was cell-cell contact dependent and partially relied on cytotoxic T lymphocyte antigen-4 expression. This approach may accelerate the clinical application of Treg-based immunotherapy in transplantation and autoimmune diseases.
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