THYMIC EXPORTATION AND EFFECTOR FUNCTION OF MEMORY-LIKE CD8+ T CELLS

VIANO, MARIA ESTEFANIA; BAIGORRÍ, RUTH ELIANA; CINTHIA STEMPIN; ANA ROSA PEREZ; BRENDA DI NATALE; FLORENCIA PACINI; CAMILA BULFONI; FLORENCIA GONZALEZ; NICOLAS LIDON; CERBAN, FABIO; RODRIGUEZ-GALAN, MARIA CECILIA

Congreso; REUNIÓN DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2022

Memory-like cells are a subset of CD8+ T cells that present a memoryphenotype without previous antigen encounter. They are a heterogeneousgroup of cells compose of innate CD8+ T cells that arisein the thymus (TIM) and are exported to secondary lymphoid organs(SLO) or, could develop directly in SLO where are named as virtualCD8+ T cells (TVM). TVM/TIM rapidly respond to IL-12 and IL-18 andplay a protective role during the early phase of bacteria, viral andparasite infections. We have previously reported that thymi from Trypanosomacruzi (Tc)-infected mice are highly enriched on TIM. TVM/TIM can be distinguished from conventional memory T cells (TMEM)by their low expression of CD49d. While residing in the thymus,phenotypic analysis in OT-I mice demonstrate that OVA tetramer+(OVAt+) single positive CD8 (SP8) cells (not specific for the parasite)expressed higher levels of CD44, CD122, CD5, CD69, Qa2 and decreasedlevels of CD24 compared to conventional polyclonal SP8cells (p<0,05). These features are in accordance with a TIM phenotype.Moreover, this pattern is even more pronounced after Tc infection(p<0,05). During exportation, our data demonstrate that CD8+ Tcells generated in the thymus can accumulate in SLO up to 5 daysafter intrathymic staining with eFluor660 (eF) dye used for tracking(p<0,05). However, these experiments demonstrated that after Tcinfection, a lower number of CD8+eF+ T cells can be found in SLO,although with a higher expression of CD44 and CD49d compared tocontrol mice (p<0,05). Functionally, splenic TVM/TIM obtained at day2 post-Tc infection produce high and similar levels of IFNg in vitroin the presence of IL-12+IL-18 than TVM/TIM from control mice Surprisingly,splenic TMEM from Tc-infected mice show significantly lower percentage of IFNg+ cells than their control counterpart (p<0,05).Our data contribute to understanding the protective role of Ag-dependentand -independent CD8+ T cells early during Tc infection.