The Contribution of Non-Conventional T Cells and NK Cells in the Mycobacterial-Specific IFNγ Response in Bacille Calmette-Guérin (BCG)-Immunized Infants

Zufferey, Christel; Germano, Susie; Dutta, Binita; Ritz, Nicole; Curtis, Nigel

doi:10.1371/journal.pone.0077334

Cited by 64 publications

(53 citation statements)

References 55 publications

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“…These enriched CD4 Ϫ CD8 Ϫ TCR-␣␤ ϩ T cells had significantly higher mRNA levels for IFN-␥ and IL-2, highlighting the need to look for correlates of protection in nontraditional CD4 ϩ and CD8 ϩ T cells. In support of this, IFN-␥-expressing DN T cells were observed in BCG-immunized children (78).…”

Section: Cd4 ؊ Cd8 ؊ Dn T Cells a Rare Subset Of T Cells That Are Cd3mentioning

confidence: 58%

Quest for Correlates of Protection against Tuberculosis

Bhatt

Verma

Ellner

et al. 2015

Clin. Vaccine Immunol.

122

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A major impediment to tuberculosis (TB) vaccine development is the lack of reliable correlates of immune protection or biomarkers that would predict vaccine efficacy. Gamma interferon (IFN-␥) produced by CD4 ؉ T cells and, recently, multifunctional CD4 ؉ T cells secreting IFN-␥, tumor necrosis factor (TNF), and interleukin-2 (IL-2) have been used in vaccine studies as a measurable immune parameter, reflecting activity of a vaccine and potentially predicting protection. However, accumulating experimental evidence suggests that host resistance against Mycobacterium tuberculosis infection is independent of IFN-␥ and TNF secretion from CD4 ؉ T cells. Furthermore, the booster vaccine MVA85A, despite generating a high level of multifunctional CD4؉ T cell response in the host, failed to confer enhanced protection in vaccinated subjects. These findings suggest the need for identifying reliable correlates of protection to determine the efficacy of TB vaccine candidates. This article focuses on alternative pathways that mediate M. tuberculosis control and their potential for serving as markers of protection. The review also discusses the significance of investigating the natural human immune response to M. tuberculosis to identify the correlates of protection in vaccination.

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Section: Cd4 ؊ Cd8 ؊ Dn T Cells a Rare Subset Of T Cells That Are Cd3mentioning

confidence: 58%

Quest for Correlates of Protection against Tuberculosis

Bhatt

Verma

Ellner

et al. 2015

Clin. Vaccine Immunol.

122

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“…A previous study reported BCG-induced unconventional CD4 − CD8 − T cells, including γδ T cells and possibly NK cells, in 10-week old infants with no prior mycobacterial sensitization who had received BCG at birth (46). Since BCG-induced conventional CD4 and CD8 T cell response peaks at 10 weeks of age (47), it is possible that BCG-reactive recall response by unconventional cells was indirectly activated by cytokines expressed by BCG-specific conventional T cells.…”

Section: Discussionmentioning

confidence: 99%

Bacillus Calmette–Guérin (BCG) Revaccination of Adults with Latent Mycobacterium tuberculosis Infection Induces Long-Lived BCG-Reactive NK Cell Responses

Suliman

Geldenhuys

Johnson

et al. 2016

The Journal of Immunology

129

139

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One third of the global population is estimated to be latently infected with Mycobacterium tuberculosis (M.tb). We performed a phase 1 randomized, controlled trial of isoniazid preventive therapy (IPT) before re-vaccination with Bacille Calmette-Guerin (BCG) in healthy, tuberculin skin test positive (≥15mm induration), HIV-negative, South African adults. We hypothesised that pre-clearance of latent bacilli with IPT modulates BCG immunogenicity following re-vaccination. Frequencies and co-expression of IFNγ, TNFα, IL-2, IL-17, and/or IL-22 in CD4, and IFNγ-expressing CD8, γδ T, CD3+CD56+ NKT-like and NK cells in response to BCG were measured using whole blood intracellular cytokine staining and flow cytometry. We analyzed 72 participants who were BCG re-vaccinated after IPT (n=33) or without prior IPT (n=39). IPT had little effect on frequencies or cytokine co-expression patterns of M.tb- or BCG-specific responses. Re-vaccination transiently boosted BCG-specific Th1 cytokine-expressing CD4, CD8 and γδ T cells. Despite high frequencies of IFNγ-expressing BCG-reactive CD3+CD56+ NKT-like, CD3−CD56dim and CD3−CD56hi NK cells at baseline, BCG re-vaccination boosted these responses, which remained elevated up to one year after re-vaccination. Such BCG-reactive memory NK cells were induced by BCG vaccination in infants, while in vitro IFN-γ expression by NK cells upon BCG stimulation was dependent on IL-12 and IL-18. Our data suggest that isoniazid pre-clearance of M.tb bacilli has little effect on the magnitude, persistence or functional attributes of lymphocyte responses boosted by BCG re-vaccination. Our study highlights surprising durability of BCG-boosted memory NKT-like and NK cells expressing anti-mycobacterial effector molecules, which may be novel targets for TB vaccines.

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“…[17][18][19] In fact, IFNc production by these cells was greater than that of CD4 + T cells. Similarly to natural infection, cd Tcell populations expand and produce IFNc in response to BCG vaccination.…”

Section: Mycobacteria and Other Bacterial Infectionsmentioning

confidence: 91%

Emerging role of γδ T cells in vaccine‐mediated protection from infectious diseases

2019

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γδ T cells are fascinating cells that bridge the innate and adaptive immune systems. They have long been known to proliferate rapidly following infection; however, the identity of the specific γδ T cell subsets proliferating and the role of this expansion in protection from disease have only been explored more recently. Several recent studies have investigated γδ T‐cell responses to vaccines targeting infections such as Mycobacterium, Plasmodium and influenza, and studies in animal models have provided further insight into the association of these responses with improved clinical outcomes. In this review, we examine the evidence for a role for γδ T cells in vaccine‐induced protection against various bacterial, protozoan and viral infections. We further discuss results suggesting potential mechanisms for protection, including cytokine‐mediated direct and indirect killing of infected cells, and highlight remaining open questions in the field. Finally, building on current efforts to integrate strategies targeting γδ T cells into immunotherapies for cancer, we discuss potential approaches to improve vaccines for infectious diseases by inducing γδ T‐cell activation and cytotoxicity.

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The Contribution of Non-Conventional T Cells and NK Cells in the Mycobacterial-Specific IFNγ Response in Bacille Calmette-Guérin (BCG)-Immunized Infants

Cited by 64 publications

References 55 publications

Quest for Correlates of Protection against Tuberculosis

Quest for Correlates of Protection against Tuberculosis

Bacillus Calmette–Guérin (BCG) Revaccination of Adults with Latent Mycobacterium tuberculosis Infection Induces Long-Lived BCG-Reactive NK Cell Responses

Emerging role of γδ T cells in vaccine‐mediated protection from infectious diseases

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