The immune responses of central and effector memory BCG-specific CD4+ T cells in BCG-vaccinated PPD+ donors were modulated by Treg cells

Li, Li; Qiao, Dan; Zhang, Xianlan; Liu, Zhihui; Wu, Changyou

doi:10.1016/j.imbio.2010.09.003

Cited by 31 publications

(23 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Helminth infection can increase the frequency of Treg cells in mice [18,19], and in man an increase of Treg cells has been observed in Strongyloides infection in patients coinfected with HTLV-1 [20] as well as in hookworm-infected patients [21]. Furthermore, it has been shown that Treg cells can modulate the immune response in Mycobacterium bovis bacille Calmette-Guerin (BCG)-vaccinated individuals [22,23] and in patients with active TB [24]. A recent study showed that in children in Gabon, the proportion of Tregs decreased with anthelmintic treatment [25].…”

Section: Introductionmentioning

confidence: 99%

“…IFN-γ is thought to play an important role in the protective immune response against TB as indicated by the susceptibility of humans with IFN-γ signaling pathway deficiencies to TB disease [7,8]. A number of studies have previously investigated the immunomodulatory effect of helminth infection on antimycobacterial immunity (reviewed in [9] [22,23] and in patients with active TB [24]. A recent study showed that in children in Gabon, the proportion of Tregs decreased with anthelmintic treatment [25].…”

mentioning

confidence: 99%

“…Second, we compared the PBMC response by flow cytometry rather than by using diluted whole blood for the bead array assay. These two differences may explain the difference in response to ESAT6/CFP10 stimulation.Helminth infections are largely associated with Th2 immune responses [5], and few studies have shown that helminth infection can be associated with an increase of regulatory T cells (Tregs) [18,23,25,35,36]. In this study we analyzed the frequency of CD4 + FoxP3 + T cells.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mycobacterium tuberculosis‐specific CD4⁺ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB

et al. 2016

View full text Add to dashboard Cite

In many settings, adults with active or latent tuberculosis will also be coinfected with helminths. Our study aimed to investigate how anthelmintic treatment modulates antimycobacterial immunity, in a setting where helminth reinfection should not occur. Additional supporting information may be found in the online version of this article at the publisher's web-site We investigated the potential impact of helminth infection on immune responses to Mycobacterium tuberculosis (Mtb) in patients with latent Mtb infection with or without helminth infection (Strongyloides orSchistosoma IntroductionMycobacterium tuberculosis (Mtb) infects a third of the world's population, causing 1.5 million deaths a year [1,2]. In addi- Correspondence:Frederic Toulza e-mail: Frederic.Toulza@lshtm.ac.uk tion, helminth infections are estimated to affect 1.5 billion people worldwide, with the majority of these infections concentrated in developing countries where tuberculosis (TB) is endemic [3,4]. Helminth infections are reported to induce Th2 type immune responses in the host [5], and evidence suggests that Th2 cytokines may play a critical role in reducing the Th1 immune response to other infections. Protection against TB is not well understood, but Th1 T-cell responses involving interferon gamma (IFN-γ), tumor C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2016. 46: 752-761 Clinical immunology 753 necrosis factor alpha (TNF-α), and interleukin 2 (IL-2) are induced in the immune response to Mtb [6]. IFN-γ is thought to play an important role in the protective immune response against TB as indicated by the susceptibility of humans with IFN-γ signaling pathway deficiencies to TB disease [7,8]. A number of studies have previously investigated the immunomodulatory effect of helminth infection on antimycobacterial immunity (reviewed in [9] [22,23] and in patients with active TB [24]. A recent study showed that in children in Gabon, the proportion of Tregs decreased with anthelmintic treatment [25].There have been only a few studies that investigated the impact of helminth infections on T-cell immunity in patients with latent TB infection. Filaria infections were shown to reduce Th1 responses in Indian patients with latent Mtb infection (LTBI), that were increased with blockage of CTLA-4 or PD-1 [26], while anthelminth treatment increased TLR2 and TLR9 expression with an associated increase in production of proinflammatory cytokines. In Indian patients with LTBI, coincident hookworm infection reduced Mtb-specific Th1 and Th17 CD4 T cells [14]. Indian pulmonary TB patients with Wucheria or Stronglyoides also showed reduced CD4 and CD8 T-cell responses to mycobacterial antigens, which could be partly blocked with anti-IL-10 neutralizing antibodies [27].In this study, we measured the impact of anthelmintic treatment on the immune response to Mtb in LTBI in a migrant cohort in London. As United Kingdom is not a helminth endemic area, reinfection is not likely in this setting. This provides a unique opport...

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Mycobacterium tuberculosis‐specific CD4⁺ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB

et al. 2016

View full text Add to dashboard Cite

show abstract

“…One explanation for this lack of protection is the induction of regulatory T cells by the vaccine [14], [25], amongst other hypotheses [26], [27]. CD4 + CD25 + Treg cells have been found after BCG vaccination of new-borns [28] and adults [29], and CD4 + CD25 + -depleted T-cell cultures resulted in lower PPD-stimulated IL-10 levels [28]. We previously demonstrated the presence and strong suppressive activity of CD8 + Treg cells among live BCG-stimulated PBMCs of in vitro PPD-responsive donors, which were enriched for the markers lymphocyte activation gene-3 (LAG-3) [30] and CD39 [31].…”

Section: Introductionmentioning

confidence: 99%

CD8+ Regulatory T Cells, and Not CD4+ T Cells, Dominate Suppressive Phenotype and Function after In Vitro Live Mycobacterium bovis-BCG Activation of Human Cells

et al. 2014

View full text Add to dashboard Cite

Mycobacterium bovis bacillus Calmette-Guérin (M. bovis BCG), the only currently available vaccine against tuberculosis, has been reported to induce regulatory T cells in humans. The activity of regulatory T cells may not only dampen immunogenicity and protective efficacy of tuberculosis-vaccines, but also hamper diagnosis of infection of tuberculosis, when using immune (e.g. IFNγ-release) assays. Still, in settings of infectious diseases and vaccination, most studies have focused on CD4+ regulatory T cells, and not CD8+ regulatory T-cells. Here, we present a comparative analysis of the suppressive phenotype and function of CD4+ versus CD8+ T cells after in vitro live BCG activation of human cells. Moreover, as BCG is administered as a (partly) live vaccine, we also compared the ability of live versus heatkilled BCG in activating CD4+ and CD8+ regulatory T cell responses. BCG-activated CD8+ T cells consistently expressed higher levels of regulatory T cell markers, and after live BCG activation, density and (co-)expression of markers were significantly higher, compared to CD4+ T cells. Furthermore, selection on CD25-expression after live BCG activation enriched for CD8+ T cells, and selection on co-expression of markers further increased CD8+ enrichment. Ultimately, only T cells activated by live BCG were functionally suppressive and this suppressive activity resided predominantly in the CD8+ T cell compartment. These data highlight the important contribution of live BCG-activated CD8+ Treg cells to immune regulation and emphasize their possible negative impact on immunity and protection against tuberculosis, following BCG vaccination.

show abstract

“…ϩ Tregs in newborns (23) and adults (24). Here, in a small, well-defined cohort of pre- degrees of skin inflammation at the vaccination site 12 weeks after BCG vaccination (left photograph, cumulative inflammation score of 3; right photograph, cumulative inflammation score of 11).…”

mentioning

confidence: 99%

Mycobacterium bovis BCG Vaccination Induces Divergent Proinflammatory or Regulatory T Cell Responses in Adults

Boer¹,

Prins²,

Meijgaarden³

et al. 2015

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

T uberculosis (TB), caused by Mycobacterium tuberculosis, is the second greatest infectious cause of death worldwide after HIV, accounting for 1.3 million deaths in 2012 (1). The only available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), protects infants from disseminated forms of TB but has insufficient and inconsistent efficacy in protecting adults from pulmonary TB (1, 2). A vaccine preventing active pulmonary TB, the contagious form of the disease, would greatly impact the epidemic (3), and a better understanding of vaccine-induced mechanisms of protection is essential in developing new surrogate endpoints (4).Both CD4 ϩ Th1 (gamma interferon-positive [IFN-␥ ϩ ]) cells and CD8 ϩ T cells are critical for protection against TB (5). Specifically, CD4ϩ IFN-␥ ϩ interleukin 2-positive (IL-2 ϩ ) tumor necrosis factor ␣-positive (TNF-␣ ϩ ) polyfunctional T cells have been proposed as a correlate of vaccine-induced protective immunity in murine infection models (6). In infants, BCG vaccination induced specific cytokine expression in CD4 ϩ and CD8 ϩ T cells (7-9), including IFN-␥ ϩ IL-2 ϩ TNF-␣ ϩ polyfunctional CD4 ϩ T cells (10). However, there was no relation between the presence of such cells and the development of TB during follow-up (11).In adults, BCG vaccination induced CD4 ϩ IFN-␥ ϩ responses (12-14) as well as IFN-␥-and TNF-␣-secreting CD8 ϩ T cells with cytotoxic activity (15). However, data on the induction of polyfunctional T cells by BCG vaccination in adults have been conflicting (16,17). In one report, the induction of polyfunctional CD4 ϩ T cells was similar in magnitude in BCG-vaccinated infants and adults; however, when induction was analyzed as the proportion of polyfunctional versus single-cytokine-producing T cells, the proportion of polyfunctional CD4 ϩ T cells was larger in children than in adults (16). Further, studies on latent (controlled) versus active TB in adults yielded variable results on changes in monoand triple-cytokine-producing T cell subsets (18,19), such that it was suggested that polyfunctional T cells are also present in active TB disease and that these cells are not a surrogate marker of protection against TB in humans (19,20).Another explanation for the inconsistent protection induced by BCG against TB in adults is the induction of regulatory T cells (Tregs) by mycobacteria, which can dampen proinflammatory responses (21). In that context, we reported that live BCG triggers the specific activation of CD8 ϩ (but not CD4 ϩ ) Tregs from peripheral blood mononuclear cells (PBMCs) of mycobacterial purified protein derivative (PPD)-responsive adults (22), while others found that BCG vaccination induced CD4 ϩ Tregs in newborns (23) and adults (24). Here, in a small, well-defined cohort of pre-

show abstract

The immune responses of central and effector memory BCG-specific CD4+ T cells in BCG-vaccinated PPD+ donors were modulated by Treg cells

Cited by 31 publications

References 35 publications

Mycobacterium tuberculosis‐specific CD4⁺ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB

Mycobacterium tuberculosis‐specific CD4⁺ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB

CD8+ Regulatory T Cells, and Not CD4+ T Cells, Dominate Suppressive Phenotype and Function after In Vitro Live Mycobacterium bovis-BCG Activation of Human Cells

Mycobacterium bovis BCG Vaccination Induces Divergent Proinflammatory or Regulatory T Cell Responses in Adults

Contact Info

Product

Resources

About

The immune responses of central and effector memory BCG-specific CD4+ T cells in BCG-vaccinated PPD+ donors were modulated by Treg cells

Cited by 31 publications

References 35 publications

Mycobacterium tuberculosis‐specific CD4+ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB

Mycobacterium tuberculosis‐specific CD4+ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB

CD8+ Regulatory T Cells, and Not CD4+ T Cells, Dominate Suppressive Phenotype and Function after In Vitro Live Mycobacterium bovis-BCG Activation of Human Cells

Mycobacterium bovis BCG Vaccination Induces Divergent Proinflammatory or Regulatory T Cell Responses in Adults

Contact Info

Product

Resources

About

Mycobacterium tuberculosis‐specific CD4⁺ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB

Mycobacterium tuberculosis‐specific CD4⁺ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB