title: Perturbed T cell IL-7 receptor signaling in chronic Chagas disease.
abstract: 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.
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires 1063, Argentina; Hospital Interzonal General de Agudos Eva Perón, 1650 San Martin, Buenos Aires, Argentina; and.
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Albareda
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires 1063, Argentina;
authors.forename: Damián
authors.initials: D
authors.lastname: Perez-Mazliah
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires 1063, Argentina;
authors.forename: M Ailén
authors.initials: MA
authors.lastname: Natale
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires 1063, Argentina;
authors.forename: Melisa
authors.initials: M
authors.lastname: Castro-Eiro
authors.affiliation: Hospital Interzonal General de Agudos Eva Perón, 1650 San Martin, Buenos Aires, Argentina; and.
authors.forename: María G
authors.initials: MG
authors.lastname: Alvarez
authors.affiliation: Hospital Interzonal General de Agudos Eva Perón, 1650 San Martin, Buenos Aires, Argentina; and.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Viotti
authors.affiliation: Hospital Interzonal General de Agudos Eva Perón, 1650 San Martin, Buenos Aires, Argentina; and.
authors.forename: Graciela
authors.initials: G
authors.lastname: Bertocchi
authors.affiliation: Hospital Interzonal General de Agudos Eva Perón, 1650 San Martin, Buenos Aires, Argentina; and.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lococo
authors.affiliation: Center for Tropical and Emerging Global Diseases, Athens, GA 30602.
authors.forename: Rick L
authors.initials: RL
authors.lastname: Tarleton
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires 1063, Argentina; Hospital Interzonal General de Agudos Eva Perón, 1650 San Martin, Buenos Aires, Argentina; and slaucella@yahoo.com.
authors.forename: Susana A
authors.initials: SA
authors.lastname: Laucella
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000276:immunology*; D050799:STAT5 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: C000595707:BCL2 protein, human; C507941:IL2RG protein, human; C508605:IL7 protein, human; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor