CD4+ T cells from chronic Chagas disease patients with different degrees of cardiac compromise exhibit distinct expression patterns of inhibitory receptors TIGIT, Tim-3 and Lag-3

Abstract T cells are central to adaptive immune response against T. cruzi infection. In the chronic stage of Chagas disease, circulating parasite-specific memory T cells show reduced functionality and increased expression of inhibitory receptors, possibly as a result of persistent antigenic stimulation. This exhausted phenotype has been linked to progression of cardiac pathology while, contrariwise, the presence of polyfunctional T cells shows association with therapeutic success and more efficient control of infection. Given this, we hypothesized that inhibitory receptors TIGIT, Tim-3 and Lag-3 may be involved in immune modulation of anti- T. cruzi T cell response, and therefore may play a role in the containment or the unleashing of inflammatory phenomena that ultimately lead to tissue damage and pathology. In this preliminary study, we assess the frequency of CD4 + T cells expressing each of these receptors and their relation to cellular activation. Samples from chronic Chagas disease patients with different degrees of cardiac compromise, and non-infected donors were analyzed under different stimulation conditions. Our results show that the frequency of TIGIT + CD4 + T cells is increased in Chagas patients, while Tim-3 + cells are more abundant in patients with signs of cardiac alterations. In addition, the frequency of Lag-3 + cells increases in non-activated CD4 + T cells from Chagas patients without demonstrable cardiopathy upon pathogen-specific in vitro antigenic stimulation.