Half-truths and selective memory: Interferon gamma, CD4+ T cells and protective memory against tuberculosis

Goldsack, Lisa; Kirman, Joanna R.

doi:10.1016/j.tube.2007.07.001

Cited by 84 publications

(73 citation statements)

References 67 publications

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“…Moreover, IFN-␥ is considered another key readout, and this obviously differs between AE T, T EM , and T CM populations, in both quantity and kinetics. Indeed, both our recent studies (17) and those of others (42) seem to indicate that in the context of memory immunity, at least, this is not always a reliable marker, and a recent review on this topic reaches a similar conclusion (10). FIG.…”

Section: Vol 17 2010 Memory T Cells In Tuberculosis Infection 623mentioning

confidence: 59%

Phenotypic Definition of Effector and Memory T-Lymphocyte Subsets in Mice Chronically Infected withMycobacterium tuberculosis

Henao-Tamayo

Ordway

Irwin

et al. 2010

Clin Vaccine Immunol

106

108

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The bacterium Mycobacterium tuberculosis remains one of the world's most successful pathogens, a situation that is aggravated by the fact that the existing vaccine, Mycobacterium bovis BCG, is not effective in adults. As with any vaccine, the purpose of giving BCG vaccination is to establish a long-lived state of memory immunity, but whether this is successfully completely established is still unclear. It is generally accepted that memory T cells can be divided into central and effector memory populations by function and by phenotype; however, the majority of data supporting this division have been generated using transgenic mouse models or mice that have recovered from acute viral infections. Tuberculosis, on the other hand, represents a persistent, chronic state of immunity in which the presence of memory T cells is far less well defined. We show here that mice vaccinated with BCG or chronically infected with M. tuberculosis establish antigen-specific populations of cells within the lungs that predominantly express a cellular phenotype consistent with their being effector or effector memory cells. In contrast, cells with a central memory phenotype exist in much lower numbers in the lungs but can be found in significantly larger numbers in the spleen, where they may represent a potential reservoir. These data suggest that the effector-to-central-memory T-cell transition may well be minimal in these persisting mycobacterial infections, and they support a novel hypothesis that this may explain the fundamental basis of the failure of the BCG vaccine in humans.

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Section: Vol 17 2010 Memory T Cells In Tuberculosis Infection 623mentioning

confidence: 59%

Phenotypic Definition of Effector and Memory T-Lymphocyte Subsets in Mice Chronically Infected withMycobacterium tuberculosis

Henao-Tamayo

Ordway

Irwin

et al. 2010

Clin Vaccine Immunol

106

108

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“…An interesting observation was that incubation at fever-range temperatures seemed to have a greater effect in patients with an ongoing infection. This might be due to the fact that the TB10.4 response in healthy individuals is likely to derive mainly from central memory T cells (2,11), whereas the TB antigen responses in patients with ongoing infection is derived from effector memory T cells (20,31,36). However, this study does not shed light on the exact mechanisms underlying the findings.…”

Section: Discussionmentioning

confidence: 73%

Incubation of Whole Blood at 39°C Augments Gamma Interferon (IFN-γ)-Induced Protein 10 and IFN-γ Responses to Mycobacterium tuberculosis Antigens

Aabye

Ravn

Johansen

et al. 2011

Clin Vaccine Immunol

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A rarely challenged dogma in cell-mediated immune (CMI) assays is the incubation temperature, 37°C. Fever augments proinflammatory immune responses in vivo, and the aim of this study was to explore whether incubation at fever-range temperature could increase antigen-specific biomarker responses. We compared CMI responses following incubation of whole blood at 37°C and 39°C. Whole blood was obtained from (i) 34 healthy subjects whose blood was incubated with TB10. Cell-mediated immune (CMI) assays are important research tools used to monitor T cell-dependent immune responses toward antigens from, e.g., pathogens or vaccines.CMI assays rely on generation of an in vitro immune response and quantification of the proinflammatory immune response (26). In clinical medicine, CMI assays are used for the diagnosis of infections that cannot be detected with direct methods (28). An example is the diagnosis of latent infection with Mycobacterium tuberculosis, where either purified peripheral blood mononuclear cells (PBMCs) or whole blood is incubated with M. tuberculosis-specific antigens, followed by quantification of the gamma interferon (IFN-␥) response, hence the name IFN-␥ release assays (IGRAs) (3).A rarely challenged dogma in CMI assays-both in research and in diagnostic medicine-is that the incubation temperature is optimal at 37°C. Fever is a part of the innate immune response in vivo and can aid the immune defense by impairing the viability of pathogens with strict temperature preferences or by enhancing immunological reactions (reviewed in reference 38). Previous studies indicate that fever-range temperature in vivo and in vitro augments antigen presentation and coreceptor expression and skews antigen-presenting cells (APCs) toward activation, in concert with augmented T cell responsiveness and Th1 bias (5,6,17,33).One of the major challenges of CMI assays-and IGRAs, in particular-is achieving a consistent and strong response (i.e., high sensitivity) without generating nonspecific immune activation (i.e., compromising specificity).We and others have demonstrated that, compared to T cell responses, the APCs interacting with the specific T cells generate stronger chemokine and cytokine signals that could enable simpler or more sensitive readouts of CMI assays (reviewed in reference 24). In several studies, the chemokine IFN-␥-induced protein 10 (IP-10) has shown promise as a novel marker for immunodiagnosis of infection with M. tuberculosis in both children and adults (1,13,15,(21)(22)(23)30).In an attempt to further improve CMI assays, we hypothesized that incubation at fever-range temperatures in vitro could lead to an increase in proinflammatory immune responses and potentially an increase in the sensitivity of IGRA and CMI assays. Interleukin-7 (IL-7) is a cytokine that promotes survival of T cells (8, 9). IL-10 is an anti-inflammatory cytokine released by T cells and monocytes/macrophages with immune activation (25). Both IL-7 and blocking of IL-10 have previously been shown to augment IFN-␥ responses to M. tub...

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“…Increasing evidence indicates that successful M. tuberculosis immunity relies not only on Th1 but also other T cell subsets (Goldsack and Kirman, 2007;Chen et al, 2012). Regulatory T (Treg) cells sustain peripheral tolerance, inhibit chronic infection, modulate the adaptive immune response (Sakaguchi et al, 2010), and can inhibit the activity of effector cells against intracellular pathogens (Shevach, 2009) including M. tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

Prominent contribution of Th1, Th17, and Tregs to the host response during M. neoaurum infection

et al. 2016

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ABSTRACT. Nontuberculous mycobacteria are ubiquitous in outside environment and animals. As for nontuberculous mycobacteria infection, there is only limited information in humans regarding infection and the subsequent immune response, especially for Mycobacterium neoaurum. Here, haematoxylin-eosin and Ziehl-Neelsen staining were used to observe pathological changes and detect acid-fast bacilli in organ samples in mouse model. tissues. Our results indicated that 72% of CD4+ T cells appeared in the early days of infection, which was followed by a decrease to 47% by day 32, and then a rise to 76% by day 56. Moreover, we found higher frequency of IFN-g-producing CD4+ T cells and elevated mRNA expression of the transcription factor T-bet in the lungs; however, we observed lower mRNA expression of the transcription factor RORgt and lower frequency of IL-17-producing CD4+ T cells. A transient relative decrease in the number of Treg cells was observed in the lungs; however, the number of Tregs did not change significantly between the first and last day following infection. Thus, M. neoaurum causes chronic infection in C57BL/6 mice, with Th1, Th17, and Tregs playing a prominent role in the host response. The present study may lay the basis for further studies on the mechanisms underlying infection with nontuberculous mycobacteria.

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Half-truths and selective memory: Interferon gamma, CD4+ T cells and protective memory against tuberculosis

Cited by 84 publications

References 67 publications

Phenotypic Definition of Effector and Memory T-Lymphocyte Subsets in Mice Chronically Infected withMycobacterium tuberculosis

Phenotypic Definition of Effector and Memory T-Lymphocyte Subsets in Mice Chronically Infected withMycobacterium tuberculosis

Incubation of Whole Blood at 39°C Augments Gamma Interferon (IFN-γ)-Induced Protein 10 and IFN-γ Responses to Mycobacterium tuberculosis Antigens

Prominent contribution of Th1, Th17, and Tregs to the host response during M. neoaurum infection

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