title: Functional analysis of killer Ig-like receptor-expressing cytomegalovirus-specific CD8+ T cells.
abstract: Killer Ig-like receptors (KIR) are expressed by human NK cells and T cells. Although Ag-specific cytolytic activity and cytokine production of KIR(+) T cells can be inhibited by KIR ligation, the effect of KIR on proliferation is unclear. KIR(+) T cells have been reported to have a general proliferative defect. To investigate whether KIR(+) T cells represent end-stage dysfunctional T cells, we characterized KIR(+) CMV-specific T cells in allogeneic stem cell transplantation patients and healthy donors. In both patients and healthy donors, a significant percentage KIR(+) T cells was detected at various time points. All stem cell transplantation patients studied showed KIR expression on CMV-specific T cells, while not all donors had KIR-expressing CMV-specific T cells. From two of the patients and one donor KIR(+) CMV-specific T clones were isolated and analyzed functionally. T cells were detected that expressed KIR that could not encounter their corresponding KIR ligands in vivo, illustrating that KIR expression by these T cells was not based on functional selection but a random process. Our data demonstrate that KIR(+) T cells are fully functional T cells that are only restricted in effector functions and proliferation upon KIR ligation. The level of KIR-mediated inhibition of the effector functions and proliferation depended on the strength of TCR stimulation. We observed no diminished general proliferative capacity and therefore we conclude that these T cells do not represent end-stage dysfunctional T cells.
authors.affiliation: Department of Hematology, Laboratory of Experimental Hematology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Lars T
authors.initials: LT
authors.lastname: van der Veken
authors.forename: Maria
authors.initials: M
authors.lastname: Diez Campelo
authors.forename: Menno A W G
authors.initials: MA
authors.lastname: van der Hoorn
authors.forename: Renate S
authors.initials: RS
authors.lastname: Hagedoorn
authors.forename: H M Esther
authors.initials: HM
authors.lastname: van Egmond
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Bergen
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D049109:Cell Proliferation; D002999:Clone Cells; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology; D054340:Receptors, KIR / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012008:Recurrence; D012190:Retroviridae / Q000235:genetics; D033581:Stem Cell Transplantation / Q000009:adverse effects; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014161:Transduction, Genetic
chemical_list: D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D054340:Receptors, KIR