Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing Tuberculosis

Feske, Marsha L.; Nudelman, Rodolfo J.; Medina, Miguel Ángel; Lew, Justin D.; Singh, Manisha; Couturier, Jacob; Graviss, Edward A.; Lewis, Dorothy E.

doi:10.1128/cvi.00185-08

Cited by 26 publications

(27 citation statements)

References 49 publications

(64 reference statements)

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“…Previous studies have demonstrated that adding IL-7 or blocking IL-10 can augment M. tuberculosis-specific antigen responsiveness in vitro (9,10,12). In the TB10.4 study, we compared anti-IL-10 and IL-7 head-to-head and found that the effects of added IL-7 appeared to be superior to those of anti-IL-10 alone.…”

Section: Discussionmentioning

confidence: 91%

“…The contents of the QFT-IT tubes comprise dextrose as the nutrient (2 mg/ml) and were added to all other cultures. Concentrations of IL-7, anti-IL-10, and dextrose were adopted from the literature (9,10,19).…”

Section: Methodsmentioning

confidence: 99%

“…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. tuberculosis-specific antigens (9,10,12).The aim of this study was to explore if incubation of cells at fever-range temperature could potentiate biomarker responses in a simple whole-blood CMI assay and if IL-7 and anti-IL-10 had an additional effect. Antigen-specific T cell responses were evaluated using IFN-␥ as marker for a T cell response and the * Corresponding author.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…We used the conditions of a previously published protocol showing increased antigen-specific IFN-γ responses if the culture medium was supplemented with IL-7 and the final volume reduced. 27 We showed that antigen expanded sensitized CD8 + T cells reduced the quantity of C. parvum in intestinal cell cultures by over 60%, whereas CD8 + T cells from a non-sensitized donor did not significantly clear the organisms. Pre-treatment of gp15 expanded sensitized effector cells with anti-CD8-antibody completely inhibited reduction of parasite load, confirming that the observed anti-parasitic effect is indeed mediated by CD8 + T cells.…”

Section: Discussionmentioning

confidence: 95%

Human CD8+ T Cells Clear Cryptosporidium parvum from Infected Intestinal Epithelial Cells

Pantenburg¹,

Castellanos-González²,

Dann³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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IL-7 Addition Increases Spot Size and Number as Measured by T-SPOT.TB ®

Feske¹,

Medina²,

Graviss³

et al. 2011

Methods in Molecular Biology

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The interferon-gamma (IFN-γ) release assay (IGRA) is an in vitro extension of the century-old in vivo tuberculin skin test, better known as the TST. Shortcomings to the TST are multifactorial and include limitations in sensitivity and specificity. IGRAs improve diagnostic specificity by using antigens not found in the Bacille Calmette-Guérin, a vaccine given in most countries. IGRAs capture the IFN-γ produced by T cells in response to antigen stimulation. The ELISPOT immediately captures IFN-γ produced directly from each cell, resulting in the generation of a cellular "footprint." The dimensions and intensity of the generated footprint indicate the avidity of the secreting cell. We show a further improvement in IGRAs by addition of interleukin-7 (IL-7). IL-7 reduces T-cell apoptosis and stabilizes IFN-γ message. In addition to increasing the number of spots in the ELISPOT T-SPOT.TB platform, IL-7 increased IFN-γ production per cell as measured by an increase in spot size with no change in spot distribution.

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Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing Tuberculosis

Cited by 26 publications

References 49 publications

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

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

Human CD8+ T Cells Clear Cryptosporidium parvum from Infected Intestinal Epithelial Cells

IL-7 Addition Increases Spot Size and Number as Measured by T-SPOT.TB ®

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