Role of naturally arising regulatory T cells in hematopoietic cell transplantation.
Naturally arising CD4(+)CD25(+) regulatory T cells (Tregs) have the potential to suppress aberrant immune responses and to regulate peripheral T-cell homeostasis. In murine models of bone marrow transplantation, Tregs promote donor bone marrow engraftment and decrease the incidence and severity of graft-versus-host-disease without abrogating the beneficial graft-versus-tumor immunologic effect. These findings, in concert with observations that Tregs in mice and humans share phenotypic and functional characteristics, have led to active investigations into the use of these cells to decrease complications associated with human hematopoietic cell transplantation. Early human studies suggest that an imbalance of Tregs and effector T cells may contribute to the development of graft-versus-host-disease. However, the mechanisms of immunoregulation, in particular the allorecognition properties of Tregs, their effects on and interaction with other immune cells, and their sites of suppressive activity, are not well understood. In this review, we discuss the current knowledge of Treg biology and the potential therapeutic strategies and barriers of Treg immunotherapy in human hematopoietic cell transplantation.
Nguyen
Vu H
VH
Center for Clinical Science Research, Department of Medicine, Division of Bone Marrow Transplantation, Stanford University, Stanford, CA 94305, USA. vunguyen@stanford.edu
Zeiser
Robert
R
Negrin
Robert S
RS
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000502:physiology; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D051193:Toll-Like Receptors / Q000502:physiology; D014181:Transplantation Immunology / Q000276:immunology*
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D051193:Toll-Like Receptors