TY - JOUR
T1 - Inhibitory receptor expression on CD8+ T cells is linked to functional responses against trypanosoma cruzi antigens in chronic chagasic patients
AU - Lasso, Paola
AU - Mateus, Jose
AU - Pavía, Paula
AU - Rosas, Fernando
AU - Roa, Nubia
AU - Thomas, M. Carmen
AU - López, Manuel C.
AU - González, John M.
AU - Puerta, Concepción J.
AU - Cuéllar, Adriana
N1 - Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc.
PY - 2015/10/15
Y1 - 2015/10/15
N2 - In mammals, chronic diseases resulting from infectious agents have been associated with functional T cell response deficiency, a high frequency of terminally differentiated T cells, the presence of monofunctional Ag-specific T cells, and increased expression of inhibitory receptors. Similar to other chronic diseases, the progressive loss of certain functional activities during Trypanosoma cruzi infection might result in the inability to control replication of this parasite. To examine this hypothesis, we evaluated the differentiation and cell effector function of CD8+ T cells and characterized the expression of inhibitory receptors and the presence of the parasite in the bloodstream of chagasic patients. The results showed that patients at an advanced severe disease stage had a higher frequency of terminally differentiated CD8+ T cells than patients at an early stage of the disease. A monofunctional CD8+ T cell response was observed in patients at an advanced stage, whereas the coexpression of markers that perform three and four functions in response to parasite Ags was observed in patients at a less severe disease stage. The frequency of CD8+ T cells producing granzyme B and perforin and those expressing inhibitory receptors was higher in symptomatic patients than in asymptomatic patients. Taken together, these findings suggest that during the course of Chagas disease, CD8+ T cells undergo a gradual loss of function characterized by impaired cytokine production, the presence of advanced differentiation, and increased inhibitory receptor coexpression.
AB - In mammals, chronic diseases resulting from infectious agents have been associated with functional T cell response deficiency, a high frequency of terminally differentiated T cells, the presence of monofunctional Ag-specific T cells, and increased expression of inhibitory receptors. Similar to other chronic diseases, the progressive loss of certain functional activities during Trypanosoma cruzi infection might result in the inability to control replication of this parasite. To examine this hypothesis, we evaluated the differentiation and cell effector function of CD8+ T cells and characterized the expression of inhibitory receptors and the presence of the parasite in the bloodstream of chagasic patients. The results showed that patients at an advanced severe disease stage had a higher frequency of terminally differentiated CD8+ T cells than patients at an early stage of the disease. A monofunctional CD8+ T cell response was observed in patients at an advanced stage, whereas the coexpression of markers that perform three and four functions in response to parasite Ags was observed in patients at a less severe disease stage. The frequency of CD8+ T cells producing granzyme B and perforin and those expressing inhibitory receptors was higher in symptomatic patients than in asymptomatic patients. Taken together, these findings suggest that during the course of Chagas disease, CD8+ T cells undergo a gradual loss of function characterized by impaired cytokine production, the presence of advanced differentiation, and increased inhibitory receptor coexpression.
UR - http://www.scopus.com/inward/record.url?scp=84943549959&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1500459
DO - 10.4049/jimmunol.1500459
M3 - Article
C2 - 26385520
AN - SCOPUS:84943549959
SN - 0022-1767
VL - 195
SP - 3748
EP - 3758
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -