Changes in leucocyte and lymphocyte subsets during tuberculosis treatment; prominence of CD3dimCD56+ natural killer T cells in fast treatment responders

Veenstra, Hanne; Baumann, Ralf; Carroll, Nora M.; Lukey, Pauline T.; Kidd, Martin; Beyers, Nulda; Bolliger, C.T.; Helden, Paul D. van; Walzl, Gerhard

doi:10.1111/j.1365-2249.2006.03144.x

Cited by 58 publications

(52 citation statements)

References 29 publications

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“…73 Interestingly, high counts of circulating CD56 ϩ T cells at diagnosis of pulmonary tuberculosis correlated significantly with negative sputum culture after 8 weeks of treatment. 74 Taken together with their expansion in a limited set of inflammatory conditions and their high effector potential (both IFN-␥ production and cytotoxicity), these data pave the way to dissect whether NK-like CD56 ϩ T cells might be critical players in the protective IL-12/23/IFN-␥-dependent immune response against Mycobacterium and Salmonella in humans.…”

Section: Discussionmentioning

confidence: 92%

A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo

Guia

Cognet

Beaucoudrey

et al. 2008

Blood

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IntroductionNatural killer (NK) cells have been initially described as non-T, non-B lymphocytes that are "naturally" elicited to mediate their effector functions (ie, cytotoxicity and cytokine production) without prior sensitization. 1 Both arms of NK cell effector functions participate in the direct innate defense and in the shaping of the adaptive immune response. 2 In several mouse models, NK cells limit the development of tumors and microbial infections. [3][4][5] In particular, NK cells control the early steps of mouse cytomegalovirus (MCMV) infection, both by directly killing virus-infected cells and by producing IFN-␥. 6 The natural acquisition of NK cell effector function has recently been challenged through the demonstration that only a minor fraction of circulating human NK cells or splenic mouse NK cells is reactive toward prototypical NK cell targets in single-cell assays. [7][8][9][10][11][12][13] It is thus becoming increasingly clear that NK cells are following various steps of maturation, culminating into the final effector stage. [10][11][12][13][14][15] In mice, the production of interleukin (IL)-15 by dendritic cells is one of the factors that primes naive NK cells into effectors. 9,13 These results suggest that the fraction of NK cells that qualifies as effectors in vitro corresponds to the NK cells that had been exposed to in vivo priming prior to the in vitro assays. This hypothesis prompted us to determine the host genetic factors that contribute to NK cell reactivity in humans. We focused our interest on the IL-12 family of cytokines, as IL-12 had been initially identified on the basis of its ability to enhance NK cell cytotoxicity and interferon-␥ (IFN-␥) production. [16][17][18][19] A number of studies have indeed demonstrated that IL-12 affects NK cell effector function, 20-23 especially with respect to NK cell activation by dendritic cells. IL-12 (IL-12p40:IL-12p35) and IL-23 (IL-12p40:IL-23p19) are structurally related heterodimeric cytokines that regulate cellmediated immune responses and Th1-type inflammatory reactions. 24 The IL-12 receptor is composed of 2 chains, IL-12R␤1 and IL-12R␤2, the former being also part of the IL-23R. 24 In mice, numerous studies have shown a critical role for IL-12 in protective immunity to various pathogens. 25 In contrast, the description of human patients with inherited IL-12 or IL-12R deficiencies has revealed that IL-12 is redundant for human defense against most Submitted November 14, 2007; accepted February 20, 2008. Prepublished online as Blood First Edition paper, March 4, 2008; DOI 10.1182 DOI 10. /blood-2007 The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. 26,27 Overall, patients with mutations in molecules involved in the IFN-␥/IL-12/23-dependent pathway are affected by the syndrome of Mendelian susceptibility to ...

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Section: Discussionmentioning

confidence: 92%

A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo

Guia

Cognet

Beaucoudrey

et al. 2008

Blood

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“…Similarly to the studies of human type 1 diabetes, investigations on the frequency of iNKT cells in human tuberculosis patients has produced contradictory results. One study reported an increase in the frequency of CD56 + CD3 + cells in TB, while two other independent studies showed a reduced frequency of Vα24 + Vβ11 + T cells or CD56 + CD3 dim cells [37,40,41]. However, none of these studies characterized iNKT cells using the more definitive approach of staining with human αGalCer/ hCD1d tetramers.…”

Section: Discussionmentioning

confidence: 99%

Alteration of the relative levels of iNKT cell subsets is associated with chronic mycobacterial infections

Kang²,

Lee³

et al. 2008

Clinical Immunology

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CD1d-restricted invariant natural killer T cells (iNKT cells) have been identified as an important type of effector and regulatory T cell, but their roles in the chronic infectious diseases caused by M. tuberculosis and M. leprae remain poorly defined. Here, we studied circulating human iNKT cells in blood samples from tuberculosis (TB) and leprosy patients. We found that the percentages of iNKT cells among total circulating T cells in TB and leprosy patients were not significantly different from those in normal controls. However, both TB and leprosy patients showed a selective reduction of the proinflammatory CD4 − CD8β − (DN) iNKT cells with a proportionate increase in the CD4 + iNKT cells. Similar phenotypic alterations in circulating iNKT cells were observed in a mouse model of M. tuberculosis infection. Taken together, these findings indicate that the selective reduction of circulating DN iNKT cells is associated with chronic infections caused by M. tuberculosis and M. leprae.

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“…Ratios of myeloid cell subpopulations in TB can vary (33)(34)(35), and this observation could explain more the abundant expression of miR-223 in active TB patients over healthy latently infected (TST + ) individuals, as well as the highest abundance of miR-223 in healthy uninfected subjects (TST -). In addition, the developmental stages at which PMNs are released into the blood stream can affect blood miR-223 levels.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment

et al. 2013

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The molecular mechanisms that control innate immune cell trafficking during chronic infection and inflammation, such as in tuberculosis (TB), are incompletely understood. During active TB, myeloid cells infiltrate the lung and sustain local inflammation. While the chemoattractants that orchestrate these processes are increasingly recognized, the posttranscriptional events that dictate their availability are unclear. We identified microRNA-223 (miR-223) as an upregulated small noncoding RNA in blood and lung parenchyma of TB patients and during murine TB. Deletion of miR-223 rendered TB-resistant mice highly susceptible to acute lung infection. The lethality of miR-223 -/-mice was apparently not due to defects in antimycobacterial T cell responses. Exacerbated TB in miR-223 -/-animals could be partially reversed by neutralization of CXCL2, CCL3, and IL-6, by mAb depletion of neutrophils, and by genetic deletion of Cxcr2. We found that miR-223 controlled lung recruitment of myeloid cells, and consequently, neutrophil-driven lethal inflammation. We conclude that miR-223 directly targets the chemoattractants CXCL2, CCL3, and IL-6 in myeloid cells. Our study not only reveals an essential role for a single miRNA in TB, it also identifies new targets for, and assigns biological functions to, miR-223. By regulating leukocyte chemotaxis via chemoattractants, miR-223 is critical for the control of TB and potentially other chronic inflammatory diseases.

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Changes in leucocyte and lymphocyte subsets during tuberculosis treatment; prominence of CD3dimCD56+ natural killer T cells in fast treatment responders

Abstract: SummaryThe immune responses against pulmonary tuberculosis are still poorly defined. This study describes changes in leucocyte and lymphocyte subsets during treatment to find reliable immunological markers for the disease and treatment response.

Cited by 58 publications

References 29 publications

A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo

A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo

Alteration of the relative levels of iNKT cell subsets is associated with chronic mycobacterial infections

MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment

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