title: Killer cell immunoglobulin-like receptor expression induction on neonatal CD8(+) T cells in vitro and following congenital infection with Trypanosoma cruzi.
abstract: Major histocompatibility complex (MHC) class I-specific inhibitory natural killer receptors (iNKRs) are expressed by subsets of T cells but the mechanisms inducing their expression are poorly understood, particularly for killer-cell immunoglobulin-like receptors (KIRs). The iNKRs are virtually absent from the surface of cord blood T cells but we found that KIR expression could be induced upon interleukin-2 stimulation in vitro. In addition, KIR expression was enhanced after treatment with 5-aza-2'-deoxycytidine, suggesting a role for DNA methylation. In vivo induction of KIR expression on cord blood T cells was also observed during a human congenital infection with Trypanosoma cruzi which triggers activation of fetal CD8(+) T cells. These KIR(+) T cells had an effector and effector/memory phenotype suggesting that KIR expression was consecutive to the antigenic stimulation; however, KIR was not preferentially found on parasite-specific CD8(+) T cells secreting interferon-gamma upon in vitro restimulation with live T. cruzi. These findings show that KIR expression is likely regulated by epigenetic mechanisms that occur during the maturation process of cord blood T cells. Our data provide a molecular basis for the appearance of KIRs on T cells with age and they have implications for T-cell homeostasis and the regulation of T-cell-mediated immune responses.
authors.affiliation: Laboratoire de Parasitologie, Faculté de Médecine, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hermann
authors.forename: Aurélie
authors.initials: A
authors.lastname: Berthe
authors.forename: Carine
authors.initials: C
authors.lastname: Truyens
authors.forename: Cristina
authors.initials: C
authors.lastname: Alonso-Vega
authors.forename: Rudy
authors.initials: R
authors.lastname: Parrado
authors.forename: Faustino
authors.initials: F
authors.lastname: Torrico
authors.forename: Yves
authors.initials: Y
authors.lastname: Carlier
authors.forename: Véronique M
authors.initials: VM
authors.lastname: Braud
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D014355:Chagas Disease / Q000151:congenital* / Q000276:immunology*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D054340:Receptors, KIR / Q000378:metabolism*; D054342:Receptors, KIR2DL1 / Q000378:metabolism; D054343:Receptors, KIR2DL2 / Q000378:metabolism; D054344:Receptors, KIR2DL3 / Q000378:metabolism; D054341:Receptors, KIR3DL1 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D007376:Interleukin-2; C515077:KIR2DL2 protein, human; C527054:KLRC1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine