apyrase and Tuberculosis

The role of CD39 pathway in Th1 cell function in tuberculosis (TB) is rarely elucidated. The present study aims to investigate the modulating mechanism of CD39 pathway during Mycobacterium tuberculosis (MTB) infection. CD39 expression was examined on host immune cells among patients with TB. The relationship between CD39 expression and Th1 cell function was analysed. Patients with TB displayed dramatically higher CD39 expression on Th1 cells than healthy controls, and a significantly increased expression of surface markers, including activation, exhaustion and apoptosis markers, were noted in CD39

Topics: Apyrase; CD4-Positive T-Lymphocytes; Cytokines; Humans; Mycobacterium tuberculosis; Th1 Cells; Tuberculosis

Correlates of death soon after antiretroviral therapy (ART) initiation remain unclear. We investigated the association between expression of CD39, a novel immune exhaustion marker, and early mortality in patients with human immunodeficiency virus/tuberculosis co-infection. Elevated pre-ART CD39+CD8+ T cell frequency was independently associated with mortality within 6 months of ART initiation.

Topics: Adult; Aged; Anti-Retroviral Agents; Antigens, CD; Antiretroviral Therapy, Highly Active; Apyrase; Biomarkers; Botswana; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes; Cohort Studies; Coinfection; Female; HIV Infections; Humans; Male; Middle Aged; Prospective Studies; Tuberculosis; Young Adult

Previous studies suggest that control of Mycobacterium tuberculosis infection is compromised by the activity of regulatory T cells, including those that express CD39, an ectonucleotidase with immunosuppressive properties. Here, we examine the role of CD39 on CD4+ T cells reacting to M. tuberculosis antigens.. Cryopreserved PBMC from patients with active TB (n = 31) or individuals with LTBI (n = 30) were cultured with PPD, ESAT-6 or CFP-10 and antigen-reactive CD4+ T cells assessed by: A) intracellular expression of interferon-gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) and interleukin (IL)-2, B) co-expression of CD25 and CD134 with or without CD39, and C) production of IFN-γ, TNF-α and IL-10 in culture supernatants.. Active TB patients were not differentiated from individuals with LTBI by intracellular expression of IFN-γ, TNF-α or IL-2 (alone or together), nor by co-expression of CD25 and CD134. However, active TB patients exhibited higher proportions of CD25+, CD134+, CD4+ T cells expressing CD39 in response to all antigens (p ≤ 0.022). Furthermore, in response to PPD, CD39 expression on CD25+, CD134+, CD4+ T cells correlated with IL-10 production (r = 0.41, p = 0.005) and inhibition of CD39 decreased IL-10 production.. Antigen-reactive CD4+ T cells expressing CD39 are more abundant in active TB than LTBI and are associated with production of the immunosuppressive cytokine IL-10. Modulating the effects of CD39 might enhance cellular immune responses against M. tuberculosis.

Topics: Adult; Antigens, Bacterial; Antigens, CD; Apyrase; Cells, Cultured; Coculture Techniques; Female; Humans; Immune Tolerance; Immunophenotyping; Interferon-gamma; Interleukin-10; Latent Tuberculosis; Lymphocyte Activation; Male; Mycobacterium tuberculosis; Phenotype; Signal Transduction; T-Lymphocytes, Regulatory; Tuberculosis; Tumor Necrosis Factor-alpha