Publication

HIV Infection Is Associated With Downregulation of BTLA Expression on Mycobacterium tuberculosis-Specific CD4T Cells in Active Tuberculosis Disease

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Last modified
  • 05/15/2025
Type of Material
Authors
    Morgan S. Barham, Emory UniversityDeborah A. Abrahams, University of Cape TownJeremiah Khayumbi, Kenya Medical Research InstituteJoshua Ongalo, Kenya Medical Research InstituteJoan Tonui, Kenya Medical Research InstituteAngela Campbell, Emory UniversityMarwou de Kock, University of Cape TownSamuel Gurrion Ouma, Kenya Medical Research InstituteFelix Hayara Odhiambo, Kenya Medical Research InstituteWillem A. Hanekom, University of Cape TownNeel Gandhi, Emory UniversityCheryl Day, Emory University
Language
  • English
Date
  • 2019-08-21
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2019 Barham, Abrahams, Khayumbi, Ongalo, Tonui, Campbell, de Kock, Ouma, Odhiambo, Hanekom, Gandhi and Day.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1664-3224
Volume
  • 10
Issue
  • AUG
Start Page
  • 1983
End Page
  • 1983
Grant/Funding Information
  • NG was supported by grants from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (K24AI114444, U19AI111211).
  • This study was supported by grants to CD from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (5R01AI083156, 5R01AI111948, U19AI111211). MB was supported by a Research Supplement to Promote Diversity in Health-Related Research from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (3R01AI111948-03S1).
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Abstract
  • Nearly a quarter of the global population is infected with Mycobacterium tuberculosis (Mtb), with 10 million people developing active tuberculosis (TB) annually. Co-infection with human immunodeficiency virus (HIV) has long been recognized as a significant risk factor for progression to TB disease, yet the mechanisms whereby HIV impairs T cell-mediated control of Mtb infection remain poorly defined. We hypothesized that HIV infection may promote upregulation of inhibitory receptors on Mtb-specific CD4 T cells, a mechanism that has been associated with antigen-specific T cell dysfunction in chronic infections. Using cohorts of HIV-infected and HIV-uninfected individuals with latent Mtb infection (LTBI) and with active TB disease, we stimulated peripheral blood mononuclear cells (PBMC) for 6 hours with Mtb peptide pools and evaluated co-expression profiles of the inhibitory receptors BTLA, CTLA-4, and PD-1 on IFN-γ+/TNF-α+ Mtb-specific CD4 T cells. Mtb-specific CD4 T cells in all participant groups expressed predominately either one or no inhibitory receptors, unlike cytomegalovirus-and HIV-specific CD4 T cells circulating in the same individuals, which were predominately CTLA-4+ PD-1+. There were no significant differences in inhibitory receptor expression profiles of Mtb-specific CD4 T cells between HIV-uninfected and HIV-infected individuals with LTBI. Surprisingly, BTLA expression, both alone and in combination with CTLA-4 and PD-1, was markedly downregulated on Mtb-specific CD4 T cells in HIV-infected individuals with active TB. Together, these data provide novel evidence that the majority of Mtb-specific CD4 T cells do not co-express multiple inhibitory receptors, regardless of HIV infection status; moreover, they highlight a previously unrecognized role of BTLA expression on Mtb-specific CD4 T cells that could be further explored as a potential biomarker of Mtb infection status, particularly in people living with HIV, the population at greatest risk for development of active TB disease.
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Keywords
Research Categories
  • Health Sciences, Immunology
  • Biology, Virology

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