2014 “Towards an HIV Cure” symposium Melbourne Following in vitro culture with myeloid dendritic cells, negative regulators of T cell activation are expressed preferentially on latently infected CD4 + T cells Vanessa A. Evans , Renée M. van der Sluis, Nitasha A. Kumar, Rafick-Pierre Sekaly, Remi Fromentin, Nicolas Chomont, Paul U. Cameron, Sharon R. Lewin
17
Embed
2014 “Towards an HIV Cure” symposium Melbourne Following in vitro culture with myeloid dendritic cells, negative regulators of T cell activation are expressed.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
2014 “Towards an HIV Cure” symposiumMelbourne
Following in vitro culture with myeloid dendritic cells, negative regulators of T cell activation are expressed preferentially on latently infected CD4+ T cellsVanessa A. Evans, Renée M. van der Sluis, Nitasha A. Kumar, Rafick-Pierre Sekaly, Remi Fromentin, Nicolas Chomont, Paul U. Cameron, Sharon R. Lewin
Infection of resting CD4+ T cells: a role for cell-cell interactions
Unactivated resting cells
Resting CD4+ T cell
Dendritic Cells
Evans et al. PLoS Pathogens 2013
Endothelial Cells
Shen et al. J Virology 2013
Ex vivo tissue blocksEckstein et al. J Virology 2001
Myeloid DC induce latency in resting memory CD4+ T cells
Productive Infection
Alone +pDC +mDC
10
100
1000
<1
****
ns
Total Cells
EG
FP
+ c
ells
/ 104
ce
lls
EG
FP
+ c
ells
/ 1
04 c
ellsAlone +pDC +mDC
1
10
100
1000
Sorted eFluor670hiEGFP-
CD4+ T cells
Latent Infection
****
Not mediated by soluble factors: CCL19, CCL21, CXCL10, IL-10, IL-6
Close DC-T cell proximity required for induction of latency
Non-proliferating CD4+ T cells
Evans et al. PLoS Pathogens 2013
Negative regulators and latency
Negative regulators dampen the immune response and can be found on exhausted T cells
Ahmed et al. J Immunol 2010; Day et al. Nature 2006
Latently infected T cells express negative regulators of T cell activation eg. PD-1, Tim-3 and TIGIT
Chomont et al. Nat Med 2010; Fromentin et al. CROI 2014
Blocking PD-L1/PD-1 in vivo restores the SIV-specific cellular and humoral immune responses, improves viral control and reduces immune activation
Velu et al. Nature 2009; Dyavar Shetty et al. J Clin Invest 2012; Finnefrock et al. J Immunol 2009
Hypothesis
Expression of negative regulators during DC-T cell interactions may actively suppress viral replication and maintain latency