دورية أكاديمية
أعرض في EDS

The presence of cytotoxic CD4 and exhausted-like CD8+ T-cells is a signature of active tuberculosis.

التفاصيل البيبلوغرافية
العنوان: The presence of cytotoxic CD4 and exhausted-like CD8+ T-cells is a signature of active tuberculosis.
المؤلفون: Flores-Gonzalez J; Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080. Mexico., Ramón-Luing LA; Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080. Mexico., Falfán-Valencia R; HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico., Batista CVF; Laboratory of Pharmacology, Escuela Militar de Graduados de Sanidad, Universidad del Ejército y Fuerza Aérea Mexicana, Mexico City 11200, Mexico., Soto-Alvarez S; Laboratory of Pharmacology, Escuela Militar de Graduados de Sanidad, Universidad del Ejército y Fuerza Aérea Mexicana, Mexico City 11200, Mexico., Huerta-Nuñez L; Laboratory of Pharmacology, Escuela Militar de Graduados de Sanidad, Universidad del Ejército y Fuerza Aérea Mexicana, Mexico City 11200, Mexico., Chávez-Galán L; Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080. Mexico. Electronic address: lchavez_galan@iner.gob.mx.
المصدر: 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.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-260X (Electronic) Linking ISSN: 09254439 NLM ISO Abbreviation: Biochim Biophys Acta Mol Basis Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier
مواضيع طبية MeSH: 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, 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
مستخلص: 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.)
فهرسة مساهمة: Keywords: CD39; Exhausted CD8+ T-cell; Tuberculosis, CD4 CTL
المشرفين على المادة: EC 3.4.21.- (Granzymes)
126465-35-8 (Perforin)
0 (Hepatitis A Virus Cellular Receptor 2)
0 (GNLY protein, human)
0 (HAVCR2 protein, human)
EC 3.4.21.- (GZMB protein, human)
0 (T-box transcription factor TBX21)
0 (T-Box Domain Proteins)
0 (Antigens, CD)
EC 3.4.21.78 (GZMA protein, human)
EC 3.6.1.5 (ENTPD1 protein, human)
0 (KLRK1 protein, human)
0 (NK Cell Lectin-Like Receptor Subfamily K)
0 (Antigens, Differentiation, T-Lymphocyte)
EC 3.6.1.5 (Apyrase)
تواريخ الأحداث: Date Created: 20240511 Date Completed: 20240615 Latest Revision: 20240628
رمز التحديث: 20240628
DOI: 10.1016/j.bbadis.2024.167219
PMID: 38734321
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-260X
DOI:10.1016/j.bbadis.2024.167219