Ex vivo expanded human CD4+CD25+Foxp3+ regulatory T cells prevent lethal xenogenic graft versus host disease (GVHD)
| Autor: | Gregory Harriman, Allis Soto, Tinghua Cao, Li Li, Steven Charles Eck, Mindi R. Walker, Wei Zhou, Weihong Wang |
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| Rok vydání: | 2009 |
| Předmět: |
Regulatory T cell
Transplantation Heterologous Immunology Cell Culture Techniques Graft vs Host Disease chemical and pharmacologic phenomena Mice SCID Nod Biology T-Lymphocytes Regulatory Mice Antigens CD immune system diseases In vivo medicine Animals Humans CTLA-4 Antigen IL-2 receptor L-Selectin Interleukin-2 Receptor alpha Subunit FOXP3 Forkhead Transcription Factors hemic and immune systems medicine.disease Transplantation surgical procedures operative medicine.anatomical_structure Graft-versus-host disease Ex vivo |
| Zdroj: | Cellular Immunology. 258:65-71 |
| ISSN: | 0008-8749 |
| DOI: | 10.1016/j.cellimm.2009.03.013 |
| Popis: | Mouse studies demonstrated that infusion of CD4+CD25+ regulatory T cells (Tregs) prevented graft versus host disease (GVHD) lethality after bone marrow transplantation (BMT). But the potential impact of human Tregs on GVHD has not been well demonstrated. In this study, we demonstrated that human Tregs enriched from peripheral blood of healthy donors could be expanded ex vivo to clinically relevant cell numbers in 2-3 weeks while maintaining Foxp3, CD25, CTLA-4, and CD62L expression as well as in vitro suppressive function. Furthermore, injection of human PBL into NOD/SCID mice induced lethal xenogenic GVHD, but co-transfer of expanded human Tregs with human PBL significantly enhanced survival, reduced GVHD symptoms, and inhibited human IgG/IgM production in the NOD/SCID mice. These results demonstrated that ex vivo expanded human Tregs retained their in vivo suppressive activity and prevented lethal xenogeneic GVHD, revealing the therapeutic potential of expanded human Tregs for GVHD. |
| Databáze: | OpenAIRE |
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