title: Role of Memory T Cells in Allograft Rejection and Tolerance.
abstract: Memory T cells are characterized by their low activation threshold, robust effector functions, and resistance to conventional immunosuppression and costimulation blockade. Unlike their naïve counterparts, memory T cells reside in and recirculate through peripheral non-lymphoid tissues. Alloreactive memory T cells are subdivided into different categories based on their origins, phenotypes, and functions. Recipients whose immune systems have been directly exposed to allogeneic major histocompatibility complex (MHC) molecules display high affinity alloreactive memory T cells. In the absence of any prior exposure to allogeneic MHC molecules, endogenous alloreactive memory T cells are regularly generated through microbial infections (heterologous immunity). Regardless of their origin, alloreactive memory T cells represent an essential element of the allograft rejection process and a major barrier to tolerance induction in clinical transplantation. This article describes the different subsets of alloreactive memory T cells involved in transplant rejection and examine their generation, functional properties, and mechanisms of action. In addition, we discuss strategies developed to target deleterious allospecific memory T cells in experimental animal models and clinical settings.
authors.affiliation: Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Gilles
authors.initials: G
authors.lastname: Benichou
authors.affiliation: Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gonzalez
authors.affiliation: Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Marino
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic , Cleveland, OH , USA.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Ayasoufi
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic , Cleveland, OH , USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Valujskikh
keywords: allotransplantation; costimulation blockade; heterologous immunity; immune suppression; memory T cells; tolerance; transplant rejection