BATF Potentially Mediates Negative Regulation of PD-1/PD-Ls Pathway on T Cell Functions in Mycobacterium tuberculosis Infection.
Front Immunol
; 10: 2430, 2019.
Article
em En
| MEDLINE
| ID: mdl-31681314
ABSTRACT
Background:
Previously, we have found that blockade of PD-1/PD-Ls pathway could enhance CD4+ T cells-mediated protective immunity in patients with active tuberculosis (ATB). However, the mechanism of PD-1/PD-Ls pathway involved in negative regulation of anti-TB immunity has been still unclear. Recently, the study of human immunodeficiency virus (HIV) infection demonstrated that PD-1 could induce the expression of basic leucine zipper ATF-like transcription factor (BATF) to inhibit CD8+ T cell function. While the mechanism of immune regulation of BATF in Mycobacterium tuberculosis (M. tb) infection has not yet been elucidated.Methods:
We enrolled 104 participants including ATB patients (n = 66), latent tuberculosis infection (LTBI) (n = 16) and healthy control (HC) (n = 22). The expressions of BATF in peripheral blood CD4+ and CD8+ T cells from enrolled subjects were determined using flow cytometry. Intervention with PD-1/PD-Ls pathway was performed by using blocking antibodies or human PD-L1 fusion protein. Silencing BATF in peripheral blood mononuclear cells (PBMCs) by electroporation with siRNA. Real-time quantitative PCR, CFSE dilution assay and enzyme linked immunosorbent assay (ELISA) were employed to test T cell functions after BATF knockdown.Results:
The percentages of BATF+CD4+ (P = 0.0003 and P < 0.0001, respectively) and BATF+CD8+ (P = 0.0003 and P = 0.0003, respectively) cells were significantly increased in ATB patients compared with LTBI and HC. BATF-expressing PD-1+ T cells in CD4+ and CD8+ T cells were much higher in ATB group than those in LTBI group (P = 0.0426 and 0.0104, respectively) and HC group (P = 0.0133 and 0.0340, respectively). There was a positive correlation between BATF expression and PD-1 expression in ATB patients (for CD4+ T cells, r = 0.6761, P = 0.0158; for CD8+ T cells, r = 0.6104, P = 0.0350). BATF knockdown could enhance IL-2 and IFN-γ secretions (P = 0.0485 and 0.0473, respectively) and CD4+ T cells proliferation (P = 0.0041) in vitro.Conclusions:
In the context of tuberculosis, BATF mediates negative regulation of PD-1/PD-Ls pathway on T cell functions. BATF knockdown can improve cytokine secretion and cells proliferation in vitro.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Tuberculose
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Linfócitos T
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Fatores de Transcrição de Zíper de Leucina Básica
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Antígeno B7-H1
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Receptor de Morte Celular Programada 1
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Mycobacterium tuberculosis
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article