Perturbed T cell IL-7 receptor signaling in chronic Chagas disease

• Published in: The Journal of immunology (1950) Vol. 194; no. 8; pp. 3883 - 3889
• Main Authors: Albareda, M Cecilia, Perez-Mazliah, Damián, Natale, M Ailén, Castro-Eiro, Melisa, Alvarez, María G, Viotti, Rodolfo, Bertocchi, Graciela, Lococo, Bruno, Tarleton, Rick L, Laucella, Susana A
• Format: Journal Article
• Language: English
• Published: United States 15.04.2015
• Subjects: Adult; Aged; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Chagas Disease - immunology; Chagas Disease - pathology; Chronic Disease; Female; Humans; Interleukin Receptor Common gamma Subunit - immunology; Interleukin-7 - immunology; Interleukin-7 Receptor alpha Subunit - immunology; Male; Middle Aged; Proto-Oncogene Proteins c-bcl-2 - immunology; Receptors, Interleukin-7 - immunology; Signal Transduction - immunology; STAT5 Transcription Factor - immunology; Trypanosoma cruzi; Trypanosoma cruzi - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1402202

We have previously demonstrated that immune responses in subjects with chronic Trypanosoma cruzi infection display features common to other persistent infections with signs of T cell exhaustion. Alterations in cytokine receptor signal transduction have emerged as one of the cell-intrinsic mechanisms of T cell exhaustion. In this study, we performed an analysis of the expression of IL-7R components (CD127 and CD132) on CD4(+) and CD8(+) T cells and evaluated IL-7-dependent signaling events in patients at different clinical stages of chronic chagasic heart disease. Subjects with no signs of cardiac disease showed a decrease in CD127(+)CD132(+) cells and a reciprocal gain of CD127(-)CD132(+) in CD8(+) and CD4(+) T cells compared with either patients exhibiting heart enlargement or uninfected controls. T. cruzi infection, in vitro, was able to stimulate the downregulation of CD127 and the upregulation of CD132 on T cells. IL-7-induced phosphorylation of STAT5 as well as Bcl-2 and CD25 expression were lower in T. cruzi-infected subjects compared with uninfected controls. The serum levels of IL-7 were also increased in chronic chagasic patients. The present study highlights perturbed IL-7/IL-7R T cell signaling through STAT5 as a potential mechanism of T cell exhaustion in chronic T. cruzi infection.