1. The presence of cytotoxic CD4 and exhausted-like CD8+ T-cells is a signature of active tuberculosis.
- Author
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Flores-Gonzalez J, Ramón-Luing LA, Falfán-Valencia R, Batista CVF, Soto-Alvarez S, Huerta-Nuñez L, and Chávez-Galán L
- 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
- 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., 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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