Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary Tuberculosis

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 HIV-seronegative 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-γ and tumor necrosis factor-α 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 Mtb-specific memory responses and active Treg cells, suggesting that susceptibility to EPTB occurs despite the ability to develop and maintain enhanced adaptive immune responses.

Tuberculosis in international immigrants: Profile and vulnerability of cases residing in the municipality of São Paulo, Brazil

“…The study identified less immigrants among those who have extrapulmonary TB, as well as with positive-microscopy of materials other than sputum. It is known that extrapulmonary TB occurs with increased frequency in persons with underlying immunodeficiency caused by other health conditions such as HIV/AIDS and diabetes mellitus, which were more prevalent in Brazilian natives ( Barreto-Duarte et al., 2020 ).…”

Identification of diagnostic biomarkers correlate with immune infiltration in extra-pulmonary tuberculosis by integrating bioinformatics and machine learning

“…CD4+ T cells can spread EPTB early, promote TB development, and maintain multi-effect functions of CD8+ T and CD3– lymphocytes (Yao et al, 2014 ). Increased memory CD4+ T cell response frequency in previously treated EPTB patients (Barreto-Duarte et al, 2020 ). Research on Memory B and dendritic cells is sparse and awaits our experimental additions.…”

Immune disturbances in female genital tuberculosis and latent genital tuberculosis

“…observed impaired cellular immunity together with increased plasma levels of cortisol and pro‐inflammatory cytokines and reduced DHEA levels in tuberculosis patients and observed increased lympho‐proliferator response and better immune endocrine scenario with anti‐tubercular therapy. In a study done in Brazil, Barreto‐Duark et al 109 . observed higher levels of CD4+ memory T cells, proliferator to Mycobacterium antigens with highest expression of CD19 on active T regulator cells in EPTB cases.…”