Functional analysis of killer Ig-like receptor-expressing cytomegalovirus-specific CD8+ T cells.
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.
van der Veken
Lars T
LT
Department of Hematology, Laboratory of Experimental Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Diez Campelo
Maria
M
van der Hoorn
Menno A W G
MA
Hagedoorn
Renate S
RS
van Egmond
H M Esther
HM
van Bergen
Jeroen
J
Willemze
Roel
R
Falkenburg
J H Frederik
JH
Heemskerk
Mirjam H M
MH
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
D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D054340:Receptors, KIR