Increased frequency of CD4+CD25+FoxP3+ circulating regulatory T cells (Treg) in tuberculous patients

Arram, Eman O.; Hassan, Rasha M.; Saleh, Mohammed A.

doi:10.1016/j.ejcdt.2013.10.013

Cited by 14 publications

(8 citation statements)

References 26 publications

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“…It has shown that T regs may protect from non-specific memory T-cell activation and potential tissue damage [ 60 ]. Hence, the reduced frequency of CD4 + T regs and the increased CD4 + /CD8 + T-cells ratio in untreated patients with ENL may explain the possibility of induction of excessive immune activation owning to the pre-existing high load of bacterial antigens in patients with lepromatous leprosy.…”

Section: Discussionmentioning

confidence: 99%

T-cell regulation in Erythema Nodosum Leprosum

et al. 2017

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Leprosy is a disease caused by Mycobacterium leprae where the clinical spectrum correlates with the patient immune response. Erythema Nodosum Leprosum (ENL) is an immune-mediated inflammatory complication, which causes significant morbidity in affected leprosy patients. The underlying cause of ENL is not conclusively known. However, immune-complexes and cell-mediated immunity have been suggested in the pathogenesis of ENL. The aim of this study was to investigate the regulatory T-cells in patients with ENL. Forty-six untreated patients with ENL and 31 non-reactional lepromatous leprosy (LL) patient controls visiting ALERT Hospital, Ethiopia were enrolled to the study. Blood samples were obtained before, during and after prednisolone treatment of ENL cases. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of regulatory T-cells by flow cytometry. Five markers: CD3, CD4 or CD8, CD25, CD27 and FoxP3 were used to define CD4+ and CD8+ regulatory T-cells. Clinical and histopathological data were obtained as supplementary information. All patients had been followed for 28 weeks. Patients with ENL reactions had a lower percentage of CD4+ regulatory T-cells (1.7%) than LL patient controls (3.8%) at diagnosis of ENL before treatment. After treatment, the percentage of CD4+regulatory T-cells was not significantly different between the two groups. The percentage of CD8+ regulatory T-cells was not significantly different in ENL and LL controls before and after treatment. Furthermore, patients with ENL had higher percentage of CD4+ T-ells and CD4+/CD8+ T-cells ratio than LL patient controls before treatment. The expression of CD25 on CD4+ and CD8+ T-cells was not significantly different in ENL and LL controls suggesting that CD25 expression is not associated with ENL reactions while FoxP3 expression on CD4+ T-cells was significantly lower in patients with ENL than in LL controls. We also found that prednisolone treatment of patients with ENL reactions suppresses CD4+ T-cell but not CD8+ T-cell frequencies. Hence, ENL is associated with lower levels of T regulatory cells and higher CD4+/CD8+ T-cell ratio. We suggest that this loss of regulation is one of the causes of ENL.

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Section: Discussionmentioning

confidence: 99%

T-cell regulation in Erythema Nodosum Leprosum

et al. 2017

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“…Despite the availability of a vaccine and an effective anti-TB therapy, TB still remains a major global health problem [ 1 ]. The predominant contributing factors to the sustained epidemic are lack of a protective vaccine, HIV infection, diagnostic difficulties and emergence of multi and extensive drug resistant strains of Mycobacterium tuberculosis (Mtb) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosis-specific plasmablast levels are differentially modulated in tuberculosis infection and disease

et al. 2020

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Background While T cell responses to Mycobacterium tuberculosis (Mtb) have been extensively studied, the role of B-cells and antibodies are less well characterised. The aim of this study was to assess levels of Mtb-specific IgG + plasmablasts across the Mtb infection spectrum. Methods Patients with active TB were analysed at baseline and 6 months of therapy (n = 20).Their exposed household contacts (HHC) included individuals with latent TB infection (LTBI; n = 20); evident at baseline; individuals with a negative Tuberculin Skin Test (TST) at baseline who became; positive at 6 months (converters; n = 11) and those who remained negative (non-converters; n = 10). An e x-vivo B-cell ELISPOT was performed to analyse plasmablast responses. Results Frequencies of ESAT-6/CFP-10 (EC)- but not Whole Cell Lysate (WCL)-specific plasmablasts were significantly higher in patients with active TB pre-treatment compared to post-treatment (p = 0.002) and compared to HHC with LTBI (p < 0.0001). Conversely, total IgG + plasmablasts were significantly decreased in TB patients at baseline. No difference was seen in levels of plasmablasts between TST converters and non-converters at baseline. Conclusions We show that EC-specific plasmablast levels are differentially modulated during TB infection and disease, with levels highest during active TB. These data provide new insights into TB biomarker development and avenues for novel immune interventions.

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“…It was shown that PlTB patients present an increased frequency of Th17 and polyfunctional effector memory T cells in the pleural cavity in comparison to blood (16,17). Apart from this effector response, regulatory T cells (Tregs), which act by bringing down the enhanced immune-mediated damage (18), have also been reported in pleural fluid from PlTB patients (16,19,20). These observations provide strong pieces of evidence that cytokine-producing T cells are able to migrate into the pleural space, not only favoring accumulation of many products and components of the immune response against M. tuberculosis but also contributing to the paucibacillary nature of the disease and yet reducing tissue damage.…”

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confidence: 99%

Predominance of Th1 Immune Response in Pleural Effusion of Patients with Tuberculosis among Other Exudative Etiologies

Lisboa

Ribeiro-Alves²,

Corrêa

et al. 2019

J Clin Microbiol

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Pleural tuberculosis (PlTB), a common form of extrapulmonary TB, remains a challenge in the diagnosis among many causes of pleural effusion. We recently reported that the combinatorial analysis of interferon gamma (IFN-γ), IFN-γ-inducible protein 10 (IP-10), and adenosine deaminase (ADA) from the pleural microenvironment was useful to distinguish pleural effusion caused by TB (microbiologically confirmed or not) among other etiologies. In this cross-sectional cohort study, a set of inflammatory mediators was quantified in blood and pleural fluid (PF) from exudative pleural effusion cases, including PlTB (n = 27) and non-PlTB (nTB) (n = 25) patients. The levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, IFN-γ, tumor necrosis factor (TNF), IP-10, transforming growth factor β1 (TGF-β), and ADA were determined using cytometric bead assay, enzyme-linked immunosorbent assay (ELISA), or biochemical tests. IFN-γ, IP-10, TNF, TGF-β, and ADA quantified in PF showed significantly higher concentrations in PlTB patients than in nTB patients. When blood and PF were compared, significantly higher concentrations of IL-6 and IL-10 in PF were identified in both groups. TGF-β, solely, showed significantly increased levels in PF and blood from PlTB patients when both clinical specimens were compared to those from nTB patients. Principal-component analysis (PCA) revealed a T helper type 1 (Th1) pattern attributed mainly to higher levels of IP-10, IFN-γ, TGF-β, and TNF in the pleural cavity, which was distinct between PlTB and nTB. In conclusion, our findings showed a predominantly cellular immune response in PF from TB cases, rather than other causes of exudative effusion commonly considered in the differential diagnosis of PlTB.

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Increased frequency of CD4+CD25+FoxP3+ circulating regulatory T cells (Treg) in tuberculous patients

Cited by 14 publications

References 26 publications

T-cell regulation in Erythema Nodosum Leprosum

T-cell regulation in Erythema Nodosum Leprosum

Mycobacterium tuberculosis-specific plasmablast levels are differentially modulated in tuberculosis infection and disease

Predominance of Th1 Immune Response in Pleural Effusion of Patients with Tuberculosis among Other Exudative Etiologies

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