Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Early IL-10 promotes vasculature-associated CD4+ T cells unable to control Mycobacterium tuberculosis infection
Catarina M. Ferreira, … , António G. Castro, Egídio Torrado
Catarina M. Ferreira, … , António G. Castro, Egídio Torrado
Published September 23, 2021
Citation Information: JCI Insight. 2021;6(21):e150060. https://doi.org/10.1172/jci.insight.150060.
View: Text | PDF
Research Article Immunology Infectious disease

Early IL-10 promotes vasculature-associated CD4+ T cells unable to control Mycobacterium tuberculosis infection

  • Text
  • PDF
Abstract

Cytokine-producing CD4+ T cells play a crucial role in the control of Mycobacterium tuberculosis infection; however, there is a delayed appearance of effector T cells in the lungs following aerosol infection. The immunomodulatory cytokine IL-10 antagonizes control of M. tuberculosis infection through mechanisms associated with reduced CD4+ T cell responses. Here, we show that IL-10 overexpression only before the onset of the T cell response impaired control of M. tuberculosis growth; during chronic infection, IL-10 overexpression reduced the CD4+ T cell response without affecting the outcome of infection. IL-10 overexpression early during infection did not, we found, significantly impair the kinetics of CD4+ T cell priming and effector differentiation. However, CD4+ T cells primed and differentiated in an IL-10–enriched environment displayed reduced expression of CXCR3 and, because they did not migrate into the lung parenchyma, their ability to control infection was limited. Importantly, these CD4+ T cells maintained their vasculature phenotype and were unable to control infection, even after adoptive transfer into low IL-10 settings. Together our data support a model wherein, during M. tuberculosis infection, IL-10 acts intrinsically on T cells, impairing their parenchymal migratory capacity and ability to engage with infected phagocytic cells, thereby impeding control of infection.

Authors

Catarina M. Ferreira, Ana Margarida Barbosa, Palmira Barreira-Silva, Ricardo Silvestre, Cristina Cunha, Agostinho Carvalho, Fernando Rodrigues, Margarida Correia-Neves, António G. Castro, Egídio Torrado

×

Figure 5

IL-10 overexpression limits CD4+ T cell migration into lung parenchyma and impairs antigen recognition and proliferation.

Options: View larger image (or click on image) Download as PowerPoint
IL-10 overexpression limits CD4+ T cell migration into lung parenchyma a...
B6 and pMT-10 mice were infected with M. tuberculosis H37Rv via aerosol route and IL-10 overexpression induced after day 5 after infection. (A) Representative immunofluorescence of CD3+ cells in lungs of mice at day 30 after infection. Scale bar: 200 μm. (B) Flow cytometry analysis and frequency of intravascular (CD45+) CD4+ T cells in lungs of mice throughout infection. (C) Flow cytometry analysis and frequency of intravascular (CD45+) IFN-γ–producing CD4+ T cells in lungs of mice at day 30 after infection. (D) Frequencies and numbers of CD69+CD4+ T cells from the lungs of mice throughout infection. (E) Frequencies and numbers of Ki-67+CD4+ T cells from lungs of mice throughout infection. Data represent 2 independent experiments with 4–5 mice per group. Data are shown as the mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001; ***P < 0.0001 using Student’s t test.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts