title: Chronic human infection with Trypanosoma cruzi drives CD4+ T cells to immune senescence.
abstract: Previously we found that the frequency of IFN-gamma-producing CD8(+) T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease along with low levels of IL-2-secreting CD8(+) T cells in all clinical stages. This impairment of the parasite-specific T cell responses was associated with phenotypic features of immune senescence of the CD8(+) T cell compartment. These data prompted us to address the question of whether the CD4(+) T cell compartment also experiences signs of exhaustion. Thus, we performed a functional and phenotypical characterization of T. cruzi-specific and overall CD4(+) T cells in chronically infected subjects with different degrees of cardiac dysfunction. The results show an inverse association between disease severity and the frequency of T. cruzi-specific IFN-gamma-producing CD4(+) T cells. The high expression of CD27 and CD28 with a relative low expression of CD57 found on CD4(+)IFN-gamma(+) T cells suggests that the effector T cell pool in chronic T. cruzi infection includes a high proportion of newly recruited T cells, but a low frequency of long-term memory cells. The total CD4(+) T cell compartment shows signs of senescence and later stages of differentiation associated with more severe stages of the disease. These findings support the hypothesis that long-term T. cruzi infection in humans might exhaust long-lived memory T cells.
authors.affiliation: Instituto Nacional de Parasitología Dr M Fatala Chaben, Buenos Aires, Argentina.
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Albareda
authors.forename: Gabriela Carina
authors.initials: GC
authors.lastname: Olivera
authors.forename: Susana A
authors.initials: SA
authors.lastname: Laucella
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Alvarez
authors.forename: Esteban Rodrigo
authors.initials: ER
authors.lastname: Fernandez
authors.forename: Bruno
authors.initials: B
authors.lastname: Lococo
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Viotti
authors.forename: Rick L
authors.initials: RL
authors.lastname: Tarleton
authors.forename: Miriam
authors.initials: M
authors.lastname: Postan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D002454:Cell Differentiation; D016922:Cellular Senescence; D014355:Chagas Disease / Q000150:complications / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013997:Time Factors; D014349:Trypanosoma cruzi
chemical_list: D007371:Interferon-gamma
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