Cell-cycle regulation of T-cell responses--novel approaches to the control of alloimmunity.
Alloreactive T cells undergo clonal expansion before they participate in allograft rejection. Current estimates suggest that roughly 1 in 20 peripheral T cells are alloreactive, and these cells may expand at least 20-50-fold during an alloimmune response in vivo. The majority of immunosuppressive drugs currently used to facilitate graft survival in experimental models and in the clinic act to inhibit T-cell proliferation. This review focuses on 1) recent advances in monitoring alloreactive T-cell proliferation during alloimmune responses, 2) the link between cell division, anergy avoidance, and effector T-cell differentiation, and 3) an overview of growth factor receptor-coupled signal transduction pathways, with emphasis on key cell-cycle regulators that may serve as potential targets for novel immunosuppressive or tolerance-inducing strategies.
Wells
Andrew D
AD
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Joseph Stokes, Jr. Research Institute, Children's Hospital of Philadelphia, 3516 Civic Center Boulevard, Philadelphia, PA 19104-4318, USA. adwells@mail.med.upenn.edu
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology
D006133:Growth Substances; D007519:Isoantigens; D017978:Receptors, Growth Factor