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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antibodies, Monoclonal / immunology
-
Antibodies, Monoclonal / pharmacology
-
Antigens, CD / metabolism
-
Azacitidine / analogs & derivatives
-
Azacitidine / pharmacology
-
CD3 Complex / immunology
-
CD8-Positive T-Lymphocytes / drug effects
-
CD8-Positive T-Lymphocytes / immunology*
-
CD8-Positive T-Lymphocytes / metabolism*
-
Chagas Disease / congenital*
-
Chagas Disease / immunology*
-
DNA Modification Methylases / antagonists & inhibitors
-
Decitabine
-
Enzyme Inhibitors / pharmacology
-
Female
-
Fetal Blood / cytology
-
Fetal Blood / immunology
-
Humans
-
Immunophenotyping
-
Infant, Newborn
-
Infant, Newborn, Diseases / immunology*
-
Interleukin-2 / pharmacology
-
NK Cell Lectin-Like Receptor Subfamily C / metabolism
-
Pregnancy
-
Receptors, Antigen, T-Cell, alpha-beta / metabolism
-
Receptors, KIR / metabolism*
-
Receptors, KIR2DL1 / metabolism
-
Receptors, KIR2DL2 / metabolism
-
Receptors, KIR2DL3 / metabolism
-
Receptors, KIR3DL1 / metabolism
-
T-Lymphocyte Subsets / immunology
-
T-Lymphocyte Subsets / metabolism
-
Trypanosoma cruzi / immunology*
Substances
-
Antibodies, Monoclonal
-
Antigens, CD
-
CD3 Complex
-
Enzyme Inhibitors
-
Interleukin-2
-
KIR2DL2 protein, human
-
KLRC1 protein, human
-
NK Cell Lectin-Like Receptor Subfamily C
-
Receptors, Antigen, T-Cell, alpha-beta
-
Receptors, KIR
-
Receptors, KIR2DL1
-
Receptors, KIR2DL2
-
Receptors, KIR2DL3
-
Receptors, KIR3DL1
-
Decitabine
-
DNA Modification Methylases
-
Azacitidine