title: Memory T cells in organ transplantation: progress and challenges.
abstract: Antigen-experienced T cells, also known as memory T cells, are functionally and phenotypically distinct from naive T cells. Their enhanced expression of adhesion molecules and reduced requirement for co-stimulation enables them to mount potent and rapid recall responses to subsequent antigen encounters. Memory T cells generated in response to prior antigen exposures can cross-react with other nonidentical, but similar, antigens. This heterologous cross-reactivity not only enhances protective immune responses, but also engenders de novo alloimmunity. This latter characteristic is increasingly recognized as a potential barrier to allograft acceptance that is worthy of immunotherapeutic intervention, and several approaches have been investigated. Calcineurin inhibition effectively controls memory T-cell responses to allografts, but this benefit comes at the expense of increased infectious morbidity. Lymphocyte depletion eliminates allospecific T cells but spares memory T cells to some extent, such that patients do not completely lose protective immunity. Co-stimulation blockade is associated with reduced adverse-effect profiles and improved graft function relative to calcineurin inhibition, but lacks efficacy in controlling memory T-cell responses. Targeting the adhesion molecules that are upregulated on memory T cells might offer additional means to control co-stimulation-blockade-resistant memory T-cell responses.
authors.affiliation: Emory University School of Medicine, Department of Surgery, 101 Woodruff Circle, #5101-WMB, Atlanta, Georgia 30322, USA.
authors.forename: Jaclyn R
authors.initials: JR
authors.lastname: Espinosa
authors.affiliation: Duke University School of Medicine, Department of Surgery, 7690 HAFS Building, Duke North Campus PO Box: 3704, Durham, North Carolina 27710, USA.
authors.forename: Kannan P
authors.initials: KP
authors.lastname: Samy
authors.affiliation: Duke University School of Medicine, Department of Surgery, 7690 HAFS Building, Duke North Campus PO Box: 3704, Durham, North Carolina 27710, USA.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Kirk
mesh_terms: D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016377:Organ Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology