Trypanosoma cruzi infection enhanced the thymic output and induce alterations in the central and peripheral V-β TCR repertoire

DINATALE B; GONZALEZ F; ARAUJO IL; BULFONI BALBI C; PACINI MF; BOTTASSO O; SAVINO W; ROGGERO E; PEREZ A

Mar del Plata

Congreso; LXX Reunión Anual de la SAI, 16-19 noviembre de 2022; 2022

Sociedad Argentina de Inmunología

The thymus is a central organ in the shaping of the peripheral T-cell repertoire. Earlier work in a murine model of Chagas disease revealed progressive thymus atrophy, characterized by CD4+CD8+(DP) loss by apoptosis. Since alterations in the normal development of T-cells or in their repertoire could influence the outcome of this infectious disease, here, we evaluated the thymic output and the V-β repertoire after T. cruzi (Tc) infection. C57BL/6 mice (n=5/group) were infected with 1000 Tc and evaluated after 17 days post-infection (dpi). Non-infected (NI) mice act as controls. The thymic output was estimated by the quantification of recent thymic emigrants (RTEs) by intrathymic injection of fluorescein (FITC), and 24 h later, thymus and subcutaneous lymph nodes (SLN) were removed and monitored for FITC+ cells occurrence. T-cell receptor excision circles (TRECs) were analyzed in blood by qPCR as RTEs markers. Repertoire screening was carried out by V-β family (5, 6, 8.1-8.2 and 14) detection by flow cytometry. In Tc mice, thymic depletion was coupled with adenomegaly. An increase in the counts of FITC+CD4+, FITC+CD8+, as well as immature and potentially autoreactive FITC+DP T-cells was observed in the SLN after 17 dpi (p