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The presence of cytotoxic CD4 and exhausted-like CD8+ T-cells is a signature of active tuberculosis.
- Source :
-
Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Aug; Vol. 1870 (6), pp. 167219. Date of Electronic Publication: 2024 May 10. - Publication Year :
- 2024
-
Abstract
- Chronic infections induce CD4+ T-cells with cytotoxic functions (CD4 CTLs); at present, it is still unknown whether latent tuberculosis (LTB) and active tuberculosis (ATB) induce CD4 CTLs. Plasma and cells from four patient groups-uninfected contact (UC), LTB, and ATB (divided as sensitive [DS-TB]- or resistant [DR-TB]-drug)-were evaluated by flow cytometry, q-PCR, and proteomics. The data showed that ATB patients had an increased frequency of CD4+ T-cells and a decreased frequency of CD8+ T-cells. The latter displays an exhausted-like profile characterized by CD39, CD279, and TIM-3 expression. ATB had a high frequency of CD4 + perforin+ cells, suggesting a CD4 CTL profile. The expression (at the transcriptional level) of granzyme A, granzyme B, granulysin, and perforin, as well as the genes T-bet (Tbx21) and NKG2D (Klrk1), in enriched CD4+ T-cells, confirmed the cytotoxic signature of CD4+ T-cells during ATB (which was stronger in DS-TB than in DR-TB). Moreover, proteomic analysis revealed the presence of HSP70 (in DS-TB) and annexin A5 (in DR-TB), which are molecules that have been associated with favoring the CD4 CTL profile. Finally, we found that lipids from Mycobacterium tuberculosis increased the presence of CD4 CTLs in DR-TB patients. Our data suggest that ATB is characterized by exhausted-like CD8+ T-cells, which, together with a specific microenvironment, favor the presence of CD4 CTLs.<br />Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Male
Adult
Female
Latent Tuberculosis immunology
Latent Tuberculosis microbiology
Middle Aged
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic metabolism
Mycobacterium tuberculosis immunology
T-Box Domain Proteins metabolism
T-Box Domain Proteins genetics
T-Box Domain Proteins immunology
Antigens, CD metabolism
Antigens, CD immunology
Antigens, CD genetics
NK Cell Lectin-Like Receptor Subfamily K metabolism
NK Cell Lectin-Like Receptor Subfamily K immunology
NK Cell Lectin-Like Receptor Subfamily K genetics
Proteomics methods
Antigens, Differentiation, T-Lymphocyte
Apyrase
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
Granzymes metabolism
Granzymes genetics
Granzymes immunology
Perforin metabolism
Perforin genetics
Perforin immunology
Hepatitis A Virus Cellular Receptor 2 metabolism
Hepatitis A Virus Cellular Receptor 2 immunology
Tuberculosis immunology
Tuberculosis microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-260X
- Volume :
- 1870
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Molecular basis of disease
- Publication Type :
- Academic Journal
- Accession number :
- 38734321
- Full Text :
- https://doi.org/10.1016/j.bbadis.2024.167219