INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Regulation of T cell response by B cells in Trypanosoma cruzi infection
MUCCI J; SOMOZA M; CAMPETELLA O
Mar del Plata, Buenos Aires
Congreso; Reunión anual de sociedades de biociencia-XXXI reunión anual de la sociedad argentina de protozoología; 2019
Previous studies in mice with partial (Xid) and absolute (μMT) deficiencies, have shown that B cells in the context of infection with T. cruzi are able to regulate the T response. However, little is known about the mechanism by which this regulation occurs. Consequently, we aimed to evaluate the modulation by B cells induced by CL Brener trypomastigotes and which are the implications in the T response. In the present work, we demonstrate that the co-culture of naive B cells (purified by CD43 negative selection) with trypomastigotes induced the proliferation of these cells and secretion of cytokines such as IL-6 and IL-10. These effects are enhanced in the presence of a CD-40 agonist ("T cell stimulus"). On the other hand, we observed that the co-culture with trypomastigotes increases the expression of MHC-II and the co-stimulatory molecules CD80 and CD86, all of which are essential for the B-T cells interaction. We have observed that IL-10 secretion by B220+ cells is associated with cells previously reported as regulatory phenotypes (marginal zone and T2-MZP). Subsequently, it was verified that the supernatant of B cells-trypomastigotes co-cultures regulate the T cell response. For this, we cultured purified naive CD4+ cells in the presence of anti-CD3/CD28 and conditioned medium from the co-cultures. A decreased proliferation accompanied with a drop in IL-2 secretion was observed. In addition, a decrease in gIFN secretion was observed together with an increase of IL-4 secretion indicating the regulation of the Th1/Th2 balance. Moreover, the co-culture of CD4+ cells together with trypomastigote-pretreated B cells induced a significant increase in the proportion of CD4+/Annexin-V+ cells, indicating an increase in their apoptosis rate. We can conclude that trypomastigote-pre-treated B cells are able to regulate the CD4+ responses by various mechanisms: inhibiting its proliferation, altering the Th1/Th2 balance and inducing apotosis.