title: Ex vivo expanded human CD4+CD25+Foxp3+ regulatory T cells prevent lethal xenogenic graft versus host disease (GVHD).
abstract: 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.
authors.affiliation: Therakos Inc., Exton, PA 19341, USA. tinghuacao@hotmail.com
authors.forename: Tinghua
authors.initials: T
authors.lastname: Cao
authors.forename: Allis
authors.initials: A
authors.lastname: Soto
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Weihong
authors.initials: W
authors.lastname: Wang
authors.forename: Steven
authors.initials: S
authors.lastname: Eck
authors.forename: Mindi
authors.initials: M
authors.lastname: Walker
authors.forename: Gregory
authors.initials: G
authors.lastname: Harriman
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D018929:Cell Culture Techniques; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D019041:L-Selectin