Invariant NKT cells from HIV-1 or Mycobacterium tuberculosis-infected patients express an activated phenotype

Montoya, Carlos; Cataño, Juan Carlos; Ramírez, Zoraida; Rugeles, Marı́a Teresa; Wilson, S. Brian; Landay, Alan

doi:10.1016/j.clim.2007.12.006

Cited by 61 publications

(68 citation statements)

References 28 publications

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“…The kinetics of depletion of CD4 ϩ CD8 Ϫ NKT cells closely mimicked those of total CD4 T-cell depletion in SHIV-infected pigtail macaques, and in general, a similar relationship has been observed in HIV-infected humans (26,34,35,37). Our results are consistent with the expression of both CXCR4 and CCR5 by macaque NKT cells (27).…”

Section: Vol 83 2009 Nkt Cells In Siv-positive Macaques 1621supporting

confidence: 86%

Peripheral NKT Cells in Simian Immunodeficiency Virus-Infected Macaques

Fernandez

Chan

Kyparissoudis

et al. 2009

J Virol

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Natural killer T (NKT) cells are important regulators of immunity for infectious diseases, tumor surveillance, allergy, and autoimmunity (2,17,36). NKT cells have a semi-invariant T-cell receptor consisting of an invariant T-cell receptor ␣ (TCR-␣) chain (V␣14-Ja18 in mice and Va24-Ja18 in humans), paired with a limited array of TCR-␤ chains (comprised of V␤8.2, V␤7, or V␤2 in mice and V␤11 in humans), that facilitates the recognition of lipid-based antigens presented by the major histocompatibility complex-like molecule CD1d. NKT cells are a potent source of cytokines and facilitate several aspects of adaptive immunity in both mice and humans.

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Section: Vol 83 2009 Nkt Cells In Siv-positive Macaques 1621supporting

confidence: 86%

Peripheral NKT Cells in Simian Immunodeficiency Virus-Infected Macaques

Fernandez

Chan

Kyparissoudis

et al. 2009

J Virol

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“…It has previously been reported that NKT cell numbers are reduced in PTB patients (33,40,42) and that NKT cell levels in LTBI subjects are comparable to those in HCs (40,42). In the present study, we classified active TB into PTB and EPTB according to infected sites.…”

Section: Discussionmentioning

confidence: 85%

“…However, much less is known about human NKT cell levels and functions in patients with M. tuberculosis infection. A numerical deficiency of NKT cells has been found in pulmonary tuberculosis (PTB) patients (33,40,42), but the NKT cell level has not been determined in extrapulmonary tuberculosis (EPTB) patients. Furthermore, the response of NKT cells to ␣-GalCer has not previously been investigated in TB patients, and the clinical relevance of NKT cell level in peripheral blood remains to be clarified.…”

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confidence: 99%

Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection

et al. 2012

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d Natural killer T (NKT) cells are known to play a protective role in the immune responses of mice against a variety of infectious pathogens. However, little is known about the detailed information of NKT cells in patients with Mycobacterium tuberculosis infection. The aims of this study were to examine NKT cell levels and functions in patients with active M. tuberculosis infection, to investigate relationships between NKT cell levels and clinical parameters, and to determine the mechanism responsible for the poor response to ␣-galactosylceramide (␣-GalCer). NKT cell levels were significantly lower in the peripheral blood of pulmonary tuberculosis and extrapulmonary tuberculosis patients, and the proliferative responses of NKT cells to ␣-GalCer were also lower in patients, whereas NKT cell levels and responses were comparable in latent tuberculosis infection subjects and healthy controls. Furthermore, this NKT cell deficiency was found to be correlated with serum C-reactive protein levels. In addition, the poor response to ␣-GalCer in M. tuberculosis-infected patients was found to be due to increased NKT cell apoptosis, reduced CD1d expression, and a defect in NKT cells. Notably, M. tuberculosis infection was associated with an elevated expression of the inhibitory programmed death-1 (PD-1) receptor on NKT cells, and blockade of PD-1 signaling enhanced the response to ␣-GalCer. This study shows that NKT cell levels and functions are reduced in M. tuberculosis-infected patients and these deficiencies were found to reflect the presence of active tuberculosis.

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“…The CD4 1 subset of iNKT cells is thought to produce both Th1 and Th2 cytokines and is thought to be less cytotoxic [13]. This subset of iNKT cells has been shown to be depleted preferentially in patients with HIV [36,37] and then restored following anti-retroviral therapy [14]. Therefore, it is possible that the CD4 1 subset of iNKT cells is playing a protective role in acute dengue, as they were more expanded in patients with DF when compared to those with DHF.…”

Section: Discussionmentioning

confidence: 99%

Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection

Kamaladasa

Wickramasinghe

Adikari

et al. 2016

Clinical and Experimental Immunology

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1These authors contributed equally to this study. SummaryInvariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)-g and interleukin (IL)24 ex-vivo enzyme-linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl-ceramide (aGalCer). We found that circulating iNKT cell proportions were significantly higher (P 5 0Á03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4 1 subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8a and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virusspecific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl-6 (P 5 0Á0003) and both Bcl-6 and inducible T cell co-stimulator (ICOS) (P 5 0Á006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4 1 iNKT cells, with reduced expression of CD161 markers.

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Invariant NKT cells from HIV-1 or Mycobacterium tuberculosis-infected patients express an activated phenotype

Cited by 61 publications

References 28 publications

Peripheral NKT Cells in Simian Immunodeficiency Virus-Infected Macaques

Peripheral NKT Cells in Simian Immunodeficiency Virus-Infected Macaques

Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection

Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection

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