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https://www.arca.fiocruz.br/handle/icict/45972
INCREASED FREQUENCY OF MEMORY CD4+ T-CELL RESPONSES IN INDIVIDUALS WITH PREVIOUSLY TREATED EXTRAPULMONARY TUBERCULOSIS
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, United States, / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, United States, / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Centro Universitário Faculdades de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Curso de Medicina. Salvador, BA, Brasil.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, United States, / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, United States, / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Centro Universitário Faculdades de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Curso de Medicina. Salvador, BA, Brasil.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / Vanderbilt University Medical Center. Vanderbilt Tuberculosis Center. Nashville. TN, USA.
Abstract
Extrapulmonary TB (EPTB) occurs with increased frequency in persons with underlying immunodeficiency. Even after recovery from acute illness, differences in immune phenotype and activation persist. Studies defining characteristics of immune responses after recovery from extrapulmonary TB may provide insights into factors that increase TB risk. We performed two case-control studies (in the United States and Brazil) among HIVseronegative adults with previous EPTB (n = 9; 25), previous pulmonary TB (n = 7; 25), latent M. tuberculosis (Mtb) infection (n = 11; 25), and uninfected TB contacts (n = 10; 25). We assessed the frequency of dual CD4+ interferon-g and tumor necrosis factor-a responses after stimulation with overlapping Mtb peptides from ESAT-6 or CFP-10, or gamma-irradiated Mtb H37Rv, proliferative responses to Mtb antigens, T-regulatory cell (Treg) frequency and phenotype. In both study populations, individuals with prior EPTB had the highest frequency of intracellular cytokine-producing cells in response to Mtb antigens (p < 0.05; p <.0001). Persons with prior EPTB in Brazil had the highest levels of CD4 proliferation to Mtb antigens (p < 0.0001), and the highest expression of CD39 on Tregs (p < 0.0001). Individuals with treated EPTB maintained high frequencies of Mtbspecific memory responses and active Treg cells, suggesting that susceptibility to EPTB occurs despite the ability to develop and maintain enhanced adaptive immune responses.
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