TY - JOUR
T1 - Fine tuning of CD8+ T-cell effector functions by targeting the 2B4-CD48
T2 - Role of the 2B4-CD48 axis in CD8+ T-cell function
AU - Lissina, Anya
AU - Ambrozak, David R
AU - Boswell, Kristin L
AU - Yang, Wenjing
AU - Boritz, Eli
AU - Wakabayashi, Yoshiyuki
AU - Iglesias, Maria Candela
AU - Hashimoto, Masao
AU - Takiguchi, Masafumi
AU - Haddad, Elias
AU - Douek, Daniel C
AU - Zhu, Jun
AU - Koup, Richard A
AU - Yamamoto, Takuya
AU - Appay, Victor
PY - 2016/7
Y1 - 2016/7
N2 - Polyfunctionality and cytotoxic activity dictate CD8+
T-cell efficacy in the eradication of infected and malignant cells. The
induction of these effector functions depends on the specific
interaction between the TCR and its cognate peptide-MHC class I complex,
in addition to signals provided by co-stimulatory or co-inhibitory
receptors, which can further regulate these functions. Among these
receptors, the role of 2B4 is contested, as it has been described as
either co-stimulatory or co-inhibitory in modulating T-cell functions.
We therefore combined functional, transcriptional and epigenetic
approaches to further characterize the impact of disrupting the
interaction of 2B4 with its ligand CD48, on the activity of human
effector CD8+ T-cell clones. In this setting, we show that the 2B4-CD48 axis is involved in the fine-tuning of CD8+ T-cell effector function upon antigenic stimulation. Blocking this interaction resulted in reduced CD8+
T-cell clone-mediated cytolytic activity, together with a subtle drop
in the expression of genes involved in effector function regulation. Our
results also imply a variable contribution of the 2B4-CD48 interaction
to the modulation of CD8+ T-cell
functional properties, potentially linked to intrinsic levels of T-bet
expression and TCR avidity. The present study thus provides further
insights into the role of the 2B4-CD48 interaction in the fine
regulation of CD8+ T-cell effector function upon antigenic stimulation.
AB - Polyfunctionality and cytotoxic activity dictate CD8+
T-cell efficacy in the eradication of infected and malignant cells. The
induction of these effector functions depends on the specific
interaction between the TCR and its cognate peptide-MHC class I complex,
in addition to signals provided by co-stimulatory or co-inhibitory
receptors, which can further regulate these functions. Among these
receptors, the role of 2B4 is contested, as it has been described as
either co-stimulatory or co-inhibitory in modulating T-cell functions.
We therefore combined functional, transcriptional and epigenetic
approaches to further characterize the impact of disrupting the
interaction of 2B4 with its ligand CD48, on the activity of human
effector CD8+ T-cell clones. In this setting, we show that the 2B4-CD48 axis is involved in the fine-tuning of CD8+ T-cell effector function upon antigenic stimulation. Blocking this interaction resulted in reduced CD8+
T-cell clone-mediated cytolytic activity, together with a subtle drop
in the expression of genes involved in effector function regulation. Our
results also imply a variable contribution of the 2B4-CD48 interaction
to the modulation of CD8+ T-cell
functional properties, potentially linked to intrinsic levels of T-bet
expression and TCR avidity. The present study thus provides further
insights into the role of the 2B4-CD48 interaction in the fine
regulation of CD8+ T-cell effector function upon antigenic stimulation.
U2 - 10.1038/icb.2016.17
DO - 10.1038/icb.2016.17
M3 - Article (Academic Journal)
C2 - 26860368
VL - 94
SP - 583
EP - 592
JO - Immunology and Cell Biology
JF - Immunology and Cell Biology
SN - 0818-9641
IS - 6
ER -