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Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167219, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38734321

RESUMO

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.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Granzimas , Receptor Celular 2 do Vírus da Hepatite A , Perforina , Tuberculose , Humanos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Masculino , Granzimas/metabolismo , Granzimas/genética , Granzimas/imunologia , Perforina/metabolismo , Perforina/genética , Perforina/imunologia , Adulto , Feminino , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Pessoa de Meia-Idade , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Mycobacterium tuberculosis/imunologia , Proteínas com Domínio T/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia , Antígenos CD/metabolismo , Antígenos CD/imunologia , Antígenos CD/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Proteômica/métodos , Antígenos de Diferenciação de Linfócitos T , Apirase
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