EFFECTORS MECHANISMS OF INNATE CD8+ T CELLS (TIM CELLS)

VIANO, ME; STEMPIN, C; BAIGORRI, RE *; CERBAN, F; RODRIGUEZ GALAN, MC

Congreso; Reunión de Sociedades de Biociencias 2021 - LXIX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2021

Innate CD8+ T cells (TIM cells) mature in the thymus as a different lineage from conventional simple positive CD8+ thymocytes 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. We have previously reported that thymi from T. cruzi-infected mice are highly enriched on TIM cells. Functionally, TIM cells act in a TCR-independent way but can exert their cytotoxic capacity through the release of perforin/granzyme. It is also postulated that TIM cells can induce cell death through the killing receptor NKG2D. NKG2D recognizes infectedcells expressing different families of ligands, especially RAE-1 receptors. However, this cytolytic mechanism is still poorly described. We evaluated the killing capacity of a bulk population of thymocytes obtained from T.cruzi-infected or control mice (efectors) when co-cultured with peritoneal macrophages (PM) infected with T.cruzi (targets). As a read-out we evaluated 48h later, the number of parasite either inside macrophages (by IF) or in the culture supernatants72h later. In both cases, we observed a reduced number of parasite when macrophages were co-cultured with T.cruzi-infected thymocytes (<0,05). Interestingly, PM stimulation with different TLR agonists demonstrate up-regulation of RAE-1g only after PolyI:C but not after LPS or PGN stimulation (<0,05). Also, PM obtained from T.cruzi-infected mice show significantly higher RAE-1g expression than PM from control mice (<0,05) becoming a possible target of NKG2D+ TIM cells.Our data intend to contribute in the understanding of the effectors mechanisms of TIM cells.