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

VIANO, MARIA ESTEFANIA; BAIGORRÍ, RUTH ELIANA; STEMPIN, CINTHIA CAROLINA; PEREZ, ANA ROSA; DI NATALE, BRENDA; PACINI, FLORENCIA; BULFONI-BALBI, CAMILA; GONZALEZ, FLORENCIA; LIDON, NICOLÁS LEONEL; CERBÁN, FABIO MARCELO; RODRIGUEZ-GALAN, MARIA CECILIA

Mar del Plata

Congreso; Reunión anual de sociedades de biociencias SAIC. SAI. SAFIS; 2022

Memory-like cells are a subset of CD8+ T cells that present a memory phenotype without previous antigen encounter. They are a heterogeneous group of cells compose of innate CD8+ T cells that arise in the thymus (TIM) and are exported to secondary lymphoid organs (SLO) or, could develop directly in SLO where are named as virtual CD8+ T cells (TVM). TVM/TIM rapidly respond to IL-12 and IL-18 and play a protective role during the early phase of bacteria, viral and parasite infections. We have previously reported that thymi from Trypanosoma cruzi (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 decreased levels of CD24 compared to conventional polyclonal SP8 cells (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+ T cells generated in the thymus can accumulate in SLO up to 5 days after intrathymic staining with eFluor660 (eF) dye used for tracking(p<0,05). However, these experiments demonstrated that after Tc infection, a lower number of CD8+eF+ T cells can be found in SLO, although with a higher expression of CD44 and CD49d compared to control mice (p<0,05). Functionally, splenic TVM/TIM obtained at day 2 post-Tc infection produce high and similar levels of IFNg in vitro in 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-dependent and -independent CD8+ T cells early during Tc infection