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

VIANO, MARIA ESTEFANIA; SAVID-FRONTERA, CONSTANZA; BAEZ, NATALIA S.; CERBÁN, FABIO; RODRIGUEZ-GALAN, MARIA CECILIA

Congreso; Reunión Anual de Sociedades de Biociencia; 2020

Sociedad Argentina de Inmunología

Innate CD8+ T cells (TIM cells) are a subset of T cells that mature in the thymus as a different lineage from conventional simple positive CD8+ thymocytes (SP8). They acquire a memory phenotype during their thymic maturation and are exported to SLO as a conventional T cell. TIM cells 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 cells mature in the thymus due to local production of IL-4 and IL-15, 2 cytokines responsible for their maturation/maintenance process. TIM cells 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 compared the expression of a large number of markers between OVA+ SP8 cells and conventional polyclonal SP8 cells simultaneously present in the thymus of control and T. cruzi infected mice. Data demonstrate that OVA+ 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). Evaluating expression of receptors that allow mature SP8 thymocyte to be exported to SLO, our data demonstrate that S1PR1 and S1PR4 are downregulated in the bulk thymocyte population from T. cruzi infected mice compared to control mice. In correlation with these data, exportation experiments performed by labeling thymocyte 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 cells that is still poorly described in the scientific literature.