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bioRxiv · 10.1101/694729

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.

Alcaraz, P. B.·Girard, M. C.·Beati, M. P.·Chadi, R. C.·Fernandez, M.·Hernandez, Y.·Gomez, K. A.·Acevedo, G.
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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.

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Alcaraz, P. B., Girard, M. C., Beati, M. P., Chadi, R. C., Fernandez, M., Hernandez, Y., Gomez, K. A., Acevedo, G.. 2019-07-08. 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.. https://doi.org/10.1101/694729

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