MITOCHONDRIAL CHARACTERIZATION OF CD8 T CELL DURING TRYPANOSOMA CRUZI INFECTION

MARÍA FLORENCIA HELLRIEGEL; ANA, YAMILE; BAIGORRÍ, RUTH ELIANA; MATÍAS EZEQUIEL VAZQUEZ VIGNALE; CERBAN, FABIO; CINTHIA STEMPIN

Congreso; REUNIÓN DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2022

We have previously demonstrated that acute T. cruzi infection triggersmitochondrial ROS (mROS) production and mitochondrial alterationsin effector (E) CD4 T cells leading to functional changes andapoptosis. Moreover, it has been shown that mitochondrial membranepotential (MMP) and mROS levels are important for E andmemory CD8 T cell function. The aim of this work was to evaluatemetabolic and mitochondrial parameters in CD8 T cells during acutephase (AP) of T. cruzi infection. Then, spleen cells were isolated fromnon-infected (NI) or AP infected BALB/c mice (with 500 trypomastigotes,at 19 days post infection). Mitochondrial parameters weremeasured by FACS in total (Tot) and E (CD44+) CD8 T cells combiningMMP-dependent (MTst) and MMP-independent mitochondrialdyes (MTgr) while mROS was tested using MitoSOX. We gated onMTgr+MTst- cells to identified T cells with depolarized mitochondriaor MTgr+MTst+ as cells with normal mitochondria. We found an increasein the frequency of CD8mROS and CD8CD44mROS producingcells in spleen of AP compared to NI mice (p<0.005;p<0.05)compatible with cell activation. However, we observed higher levelsof mROS being produced by Tot and E CD8 T cells with depolarizedmitochondria (p<0.005;p<0.001) and the frequency of these cells isincreased in AP mice (p<0.005). Next, we test if PD1 expressionis related to accumulation of depolarized mitochondria. In the APof infection, a higher proportion of E CD8 T cells express PD1 andshowed loss of MMP (MTst-PD1+) compared to cells with an activatedphenotype that had conserved MMP (MTst+PD1+)(p<0.0001).Besides, Tot and E CD8 T cells with loss of MMP and ROSm productionexhibited reduced functional activity measured by lower levelsof 2NBDG uptake, a fluorescent glucose analog, compared to cellswith conserved MMP (p<0.0005;p<0.005). These results showedthat study of mitochondrial parameters in CD8 cells could also berelevant to understand the immune response in T. cruzi infection.