Innate CD8+ T cells: from the thymus to the secondary lymphoid organs (SLO) in steady state versus Trypanosoma cruzi infection

ESTEFANIA VIANO; CONSTANZA SAVID-FRONTERA ; MARIANA MATELLON; FABIO CERBAN ; MARIA CECILIA RODRIGUEZ GALÁN

Buenos Aires

Congreso; Reunion Biociencias 2020; 2020

SAI - SAIC- SAFIS

Simple positive CD8+ thymocytes (SP8) that develop in the thymus could give rise either to conventional SP8 or to Innate CD8+ T cells (TIM). TIM acquire a memory phenotype during their thymic maturation and are exported to SLO as a conventional T cell. TIM play a protective role during the early phase of infectious processes as reported for certain bacteria, viral and parasite infections. Our previous results demonstrated that during T. cruzi infection, a large number of TIM mature in the thymus due to local production of IL-4 and IL-15, 2 cytokines responsible for their maturation/maintenance process. TIM functionally act in a TCR-independent way; instead they are activated through cytokines as IL-12 and IL-18. By using OT-I mice (not RAG2 KO, that carry an OVA specific TCR in most of SP8 cells) we could compare the expression of a large number of markers between OVA tetramer+ (OVAt+) SP8 cells (not specific for the parasite) and conventional polyclonal SP8 cells simultaneously present in the thymus of control and T. cruzi infected mice. Data demonstrate that OVAt+ SP8 cells expressed higher levels of CD44, CD122, CD5, CD69, QA2 and decreased levels of CD24 compared to conventional SP8 cells while other markers like CD62L, PD-1 and CD5 seem not to be differentially expressed (p<0,05). Moreover, this pattern is even more pronounced after T. cruzi infection (p<0,05) demonstrating that OVAt+ SP8 cells adopt a TIM phenotype in and Ag-independent way after infection. Expression of S1PR1 and S1PR4, that allow mature SP8 thymocyte to be exported to SLO, is downregulated in the bulk thymocyte population from T. cruzi-infected compared to control mice. In correlation with these data, exportation experiments performed by labeling thymocytes with CFSE (using intrathymic injection) demonstrated a significant lower number of CD8-CFSE+ cells in SLO of T. cruzi infected mice (p<0,05). Our data contribute to understand the maturation and exportation process of TIM that is still poorly described in the scientific literature.