Killer cell immunoglobulin‐like receptor expression induction on neonatal CD8⁺ T cells in vitro and following congenital infection with Trypanosoma cruzi

Abstract

Summary 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‐γ 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.

Multiplex and Genome-Wide Analyses Reveal Distinctive Properties of KIR+ and CD56+ T Cells in Human Blood

“…In this study, we confirmed prior findings that KIR + CD56 + T cells are rare (<1%) in umbilical cord blood and account for <20% of T cells in CMV-seronegative adults (60, 61). However, during CMV reactivation in an immunocompromised state such as that in transplant recipients, we found that the KIR + CD56 + T population markedly expanded in real time corresponding to viral replication.…”

Delivery of parasite Cdg7_Flc_0990 RNA transcript into intestinal epithelial cells duringCryptosporidium parvuminfection suppresses host cell gene transcription through epigenetic mechanisms

“…A diverse array of bacterial and viral effectors has been identified that either mimic or inhibit the host cellular machinery, thus facilitating the pathogen’s lifecycle. Parasite-associated epigenetic alterations in the host have been demonstrated in T cells following infection with T. cruzi (Hermann et al ., 2010) and in congenital toxoplasmosis (Jamieson et al ., 2008). Whether epigenetic trans-suppression is associated with C. parvum -induced alterations of gene expression in host epithelial cells is unclear.…”

“…Parasite-associated epigenetic alterations in the host have been demonstrated in T cells following infection with Trypanosoma cruzi (Hermann et al, 2010) and in congenital toxoplasmosis (Jamieson et al, 2008). Whether epigenetic trans-suppression is associated with FIGURE 3 Nuclear delivery of Cdg7_FLc_0990 promotes euchromatic histone lysine methyltransferase 2 (G9a)-mediated gene trans-suppression in host cells.…”

Mechanism of Congenital Chagas Disease: Effective Infection Depends on the Interplay Between Trypanosoma cruzi and the Different Tissue Compartments in the Chorionic Villi of the Human Placenta

“…Contrarily, the levels of inflammation markers and activation of NK cells are rather low in congenitally infected newborns (Hermann et al, 2010). These data highly suggest a protective role of such innate defenses in an uninfected newborn from infected mothers.…”