ArticlePLoS pathogens2018
Circulating HLA-DR+CD4+ effector memory T cells resistant to CCR5 and PD-L1 mediated suppression compromise regulatory T cell function in tuberculosis.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- T cell responses in repeated controlled human schistosome infection compared to natural exposure.Nature communications · 2025Trial
- Peptide-driven identification of TCRs reveals dynamics and phenotypes of CD4 T cells in tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Influenza vaccination post-COVID-19 expands vaccine-specific effector CD4 T-cells and Tregs under positive influence of host trained innate immunity.NPJ vaccines · 2025Article
- Immune cells display an abnormal maturation and a proinflammatory profile in telomere biology disorders.Blood advances · 2025Article
- Immunophenotyping of T Cells in Lung Malignancies and Cryptogenic Organizing Pneumonia.Journal of clinical medicine · 2025Article
- Genetically predicted immune cells mediate the association between gut microbiota and neuropathy pain.Inflammopharmacology · 2024Article
- Defining Human Regulatory T Cells beyond FOXP3: The Need to Combine Phenotype with Function.Cells · 2024Review
- ImpairedFrontiers in immunology · 2024Article
- AnFrontiers in pharmacology · 2024Article
- BCG revaccination in adults enhances pro-inflammatory markers of trained immunity along with anti-inflammatory pathways.iScience · 2023Article
- Tuberculosis and COVID-19 Dually Affect Human Th17 Cell Immune Response.Biomedicines · 2023Review
- Immunogenomic profile at baseline predicts host susceptibility to clinical malaria.Frontiers in immunology · 2023Article
- Review
- Antiretroviral therapy timing impacts latent tuberculosis infection reactivation in a Mycobacterium tuberculosis/SIV coinfection model.The Journal of clinical investigation · 2022Article
- HLA-DR Marks Recently Divided Antigen-Specific Effector CD4 T Cells in Active Tuberculosis Patients.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- CD69+ resident memory T cells are associated with graft-versus-host disease in intestinal transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Classical CD4 T cells as the cornerstone of antimycobacterial immunity.Immunological reviews · 2021Review
- AMPD1 Is Associated With the Immune Response and Serves as a Prognostic Marker in HER2-Positive Breast Cancer.Frontiers in oncology · 2021Article
- Emerging patterns of regulatory T cell function in tuberculosis.Clinical and experimental immunology · 2020Review
- Innate immune mechanisms to oral pathogens in oral mucosa of HIV-infected individuals.Oral diseases · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic T cell activation is a hallmark of pulmonary tuberculosis (PTB). The mechanisms underpinning this important phenomenon are however, poorly elucidated, though known to rely on control of T effector cells (Teff) by regulatory T cells (Treg). Our studies show that circulating natural Treg cells in adults with PTB preserve their suppressive potential but Teff cells from such subjects are resistant to Treg-mediated suppression. We found this to be due to expansion of an activated Teff subset identified by Human Leukocyte Antigen (HLA)-DR expression. Sensitivity to suppression was restored to control levels by depletion of this subset. Comparative transcriptome analysis of Teff cells that contain HLA-DR+ cells versus the fraction depleted of this population identified putative resistance mechanisms linked to IFNG, IL17A, IL22, PD-L1 and β-chemokines CCL3L3, CCL4 expression. Antibody blocking experiments confirmed HLA-DR+ Teff cells, but not the fraction depleted of HLA-DR+ effectors, to be resistant to Treg suppression mediated via CCR5 and PD-L1 associated pathways. In the presence of HLA-DR+ Teff cells, activation of NFκB downstream of CCR5 and PD-L1 was perturbed. In addition, HLA-DR+ Teff cells expressed significantly higher levels of Th1/Th17 cytokines that may regulate Treg function through a reciprocal counter-balancing relationship. Taken together, our study provides novel insight on how activated HLA-DR+CD4+ T cells may contribute to disease associated inflammation by compromising Treg-mediated suppression in PTB.
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