title: T Cells Going Innate.
abstract: Natural killer (NK) cell receptors (NKRs) play a crucial role in the homeostasis of antigen-experienced T cells. Indeed, prolonged antigen stimulation may induce changes in the receptor repertoire of T cells to a profile that features NKRs. Chronic antigen exposure, at the same time, has been shown to trigger the loss of costimulatory CD28 molecules with recently reported intensified antigen thresholds of antigen-experienced CD8(+) T cells. In transplantation, NKRs have been shown to assist allograft rejection in a CD28-independent fashion. We discuss here a role for CD28-negative T cells that have acquired the competency of the NKR machinery, potentially promoting allorecognition either through T cell receptor (TCR) crossreactivity or independently from TCR recognition. Collectively, NKRs can bring about innate-like T cells by providing alternative costimulatory pathways that gain relevance in chronic inflammation, potentially leading to resistance to CD28-targeting immunosuppressants.
authors.affiliation: Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany.
authors.forename: Midas
authors.initials: M
authors.lastname: Seyda
authors.affiliation: Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Abdallah
authors.initials: A
authors.lastname: Elkhal
authors.affiliation: Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Quante
authors.affiliation: Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, Germany.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
authors.affiliation: Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: stullius@partners.org.
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Tullius
mesh_terms: D056704:Adaptive Immunity; D000375:Aging / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000276:immunology; D018106:CD28 Antigens / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000941:Antigens; D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell; D055607:Receptors, Natural Killer Cell
keywords: NK cell receptors; T cells; adaptive immunity; innate immunity; transplantation