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

VIANO, MARIA ESTEFANIA; STEMPIN, CINTHIA; BAIGORRÍ, RUTH ELIANA; CERBÁN, FABIO; RODRIGUEZ-GALAN, MARIA CECILIA

Congreso; REUNION CONJUNTA SAIC-SAI-AAFE-NANOMED; 2021

Innate CD8+T cells (TIM cells) mature in the thymus as a different lineage from conventional simple positiveCD8+thymocytes and are exported to SLO as a conventional T cell. TIM cells play a protective role duringthe early phase of infectious processes as reported for certain bacteria, viral and parasite infections. Wehave 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 therelease of perforin/granzyme. It is also postulated that TIM cells can induce cell death through the killingreceptor NKG2D. NKG2D recognizes infected cells expressing different families of ligands, especially RAE1 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 orcontrol 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 supernatants 72h later. In both cases, we observed a reduced number of parasite whenmacrophages were co-cultured with T.cruzi-infected thymocytes (<0,05).Interestingly, PM stimulation with different TLR agonists demonstrate up-regulation of RAE-1 onlyafter PolyI:C but not after LPS or PGN stimulation (<0,05). Also, PM obtained from T.cruzi-infected miceshow significantly higher RAE-1 expression than PM from control mice (<0,05) becoming a possible targetof NKG2D+TIM cells. Our data intend to contribute in the understanding of the effectors mechanisms ofTIM cells.