STUDY OF GAMMA DELTA T LYMPHOCYTES RESPONSES TO BACTERIAL AND DAMAGE ASSOCIATED MOLECULES IN THE PRESENCE OF SHIGA TOXIN TYPE 2.

MELILLO N; ROSSO D; ROSATO M; SHIROMIZU, CM; KEITELMAN I; SABBIONE F; TREVANI A; AMARAL MM; JANCIC C

Congreso; Third French-Argentine Immunology Congress ? Reunión Anual Sociedades de Biociencias; 2022

The hemolytic uremic syndrome (HUS) mainly affects childrenyounger than 5 years old, who have a higher risk of developingsevere consequences such as acute or chronic renal failure. HUSassociated with diarrhea, hemolytic anemia, and thrombocytopeniais a consequence of Shiga toxin (Stx)-producing Escherichia coli(STEC) infection. Stx type 2 (Stx2)-producing strains are associatedwith severe cases of HUS in Argentina. γδ T cells are a specializedsubset of T cells, which act as early sensors of cellular stress andinfection. They can exert cytotoxicity against infected cells and producecytokines and chemokines. Previously, we demonstrated thatStx2-treated human glomerular endothelial cells modulate the γδT cell functions. In this work, we studied the activation of humanperipheral blood γδ T cells in response to Stx2 (0.01ng/ml), in thepresence of different agonists to emulate an inflammatory microenvironmentthat could be developed at the gut epithelial barrier.For that purpose, we used: 1) the phosphoantigen HMBPP (1μM),a potent γδ T cell bacterial agonist; 2) lipopolysaccharide (LPS:100ng/ml), an integral component of Gram-negative bacteria; and3) monosodium urate crystals (MSU: 200μg/ml) which act as molecularassociated damage pattern. To evaluate γδ T cell activation,we analyzed CD69 expression by flow cytometry, and cytokine productionby ELISA, after 24 h incubation with the agonist alone or incombination with Stx2. As result, we observed an increase in CD69expression, IFN-γ, and TNF-α production (p