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

MELILLO, NADIA C; ROSSO, DAVID A; ROSATO, MICAELA; SHIROMIZU, CAROLINA M; KEITELMAN, IRENE A; SABBIONE, FLORENCIA; TREVANI, ANALÍA; AMARAL, MARÍA MARTA; JANCIC, CAROLINA C

Mar del Plata, Buenos Aires

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

SAIC, SAI, FAIC y SAFIS

The hemolytic uremic syndrome (HUS) mainly affects children younger than 5 years old, who have a higher risk of developing severe consequences such as acute or chronic renal failure. HUS associated with diarrhea, hemolytic anemia, and thrombocytopenia is a consequence of Shiga toxin (Stx)-producing Escherichia coli (STEC) infection. Stx type 2 (Stx2)-producing strains are associated with severe cases of HUS in Argentina. γδ T cells are a specialized subset of T cells, which act as early sensors of cellular stress and infection. They can exert cytotoxicity against infected cells and produce cytokines and chemokines. Previously, we demonstrated that Stx2-treated human glomerular endothelial cells modulate the γδ T cell functions. In this work, we studied the activation of human peripheral blood γδ T cells in response to Stx2 (0.01ng/ml), in the presence of different agonists to emulate an inflammatory microenvironment that 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; and 3) monosodium urate crystals (MSU: 200µg/ml) which act as molecular associated damage pattern. To evaluate γδ T cell activation, we analyzed CD69 expression by flow cytometry, and cytokine production by ELISA, after 24 h incubation with the agonist alone or in combination with Stx2. As result, we observed an increase in CD69 expression, IFN-γ, and TNF-α production (p