Ex vivo expanded human CD4+CD25+Foxp3+ regulatory T cells prevent lethal xenogenic graft versus host disease (GVHD). 2009

Tinghua Cao, and Allis Soto, and Wei Zhou, and Weihong Wang, and Steven Eck, and Mindi Walker, and Gregory Harriman, and Li Li
Therakos Inc., Exton, PA 19341, USA. tinghuacao@hotmail.com

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.

UI MeSH Term Description Entries
D006086 Graft vs Host Disease The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION. Graft-Versus-Host Disease,Homologous Wasting Disease,Runt Disease,Graft-vs-Host Disease,Disease, Graft-Versus-Host,Disease, Graft-vs-Host,Disease, Homologous Wasting,Disease, Runt,Diseases, Graft-Versus-Host,Diseases, Graft-vs-Host,Graft Versus Host Disease,Graft-Versus-Host Diseases,Graft-vs-Host Diseases
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014183 Transplantation, Heterologous Transplantation between animals of different species. Xenotransplantation,Heterograft Transplantation,Heterografting,Heterologous Transplantation,Xenograft Transplantation,Xenografting,Transplantation, Heterograft,Transplantation, Xenograft
D015703 Antigens, CD Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation. CD Antigen,Cluster of Differentiation Antigen,Cluster of Differentiation Marker,Differentiation Antigens, Leukocyte, Human,Leukocyte Differentiation Antigens, Human,Cluster of Differentiation Antigens,Cluster of Differentiation Markers,Antigen Cluster, Differentiation,Antigen, CD,CD Antigens,Differentiation Antigen Cluster,Differentiation Marker Cluster,Marker Cluster, Differentiation
D016513 Mice, SCID Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice. SCID Mice,SCID-hu Mice,Severe Combined Immunodeficient Mice,Immunodeficient Mice, Severe Combined,Mouse, SCID,Mouse, SCID-hu,Mice, SCID-hu,Mouse, SCID hu,SCID Mouse,SCID hu Mice,SCID-hu Mouse
D050378 T-Lymphocytes, Regulatory CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells. Regulatory T Cell,Regulatory T-Cell,Regulatory T-Lymphocyte,Regulatory T-Lymphocytes,Suppressor T-Lymphocytes, Naturally-Occurring,T-Cells, Regulatory,Th3 Cells,Tr1 Cell,Treg Cell,Regulatory T-Cells,Suppressor T-Cells, Naturally-Occurring,Tr1 Cells,Treg Cells,Cell, Regulatory T,Cell, Th3,Cell, Tr1,Cell, Treg,Cells, Regulatory T,Cells, Th3,Cells, Tr1,Cells, Treg,Naturally-Occurring Suppressor T-Cell,Naturally-Occurring Suppressor T-Cells,Naturally-Occurring Suppressor T-Lymphocyte,Naturally-Occurring Suppressor T-Lymphocytes,Regulatory T Cells,Regulatory T Lymphocyte,Regulatory T Lymphocytes,Suppressor T Cells, Naturally Occurring,Suppressor T Lymphocytes, Naturally Occurring,Suppressor T-Cell, Naturally-Occurring,Suppressor T-Lymphocyte, Naturally-Occurring,T Cell, Regulatory,T Cells, Regulatory,T Lymphocytes, Regulatory,T-Cell, Naturally-Occurring Suppressor,T-Cells, Naturally-Occurring Suppressor,T-Lymphocyte, Regulatory,Th3 Cell
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051858 Forkhead Transcription Factors A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila. Forkhead Box Protein,Forkhead Box Transcription Factor,Forkhead Protein,Forkhead Transcription Factor,Forkhead Box Proteins,Forkhead Box Transcription Factors,Forkhead Proteins,Fox Transcription Factors,Box Protein, Forkhead,Box Proteins, Forkhead,Factor, Forkhead Transcription,Protein, Forkhead,Protein, Forkhead Box,Proteins, Forkhead Box,Transcription Factor, Forkhead,Transcription Factors, Forkhead,Transcription Factors, Fox
D053645 Interleukin-2 Receptor alpha Subunit A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2. Antigens, CD25,CD25 Antigens,Interleukin-2 Receptors alpha,Tac P55 Peptide,CD25 Antigen,IL-2Ralpha,Interleukin-2 Receptor alpha,Interleukin-2 Receptor alpha Chain,Interleukin-2Ralpha,alpha-subunit, Receptor, Interleukin-2,Antigen, CD25,IL 2Ralpha,Interleukin 2 Receptor alpha,Interleukin 2 Receptor alpha Chain,Interleukin 2 Receptor alpha Subunit,Interleukin 2 Receptors alpha,Interleukin 2Ralpha,Receptor alpha, Interleukin-2,Receptors alpha, Interleukin-2

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