The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus

Bernin, Hannah; Fehling, Helena; Marggraff, Claudia; Tannich, Egbert; Lotter, Hannelore

doi:10.1007/s00430-016-0449-y

Cited by 38 publications

(22 citation statements)

References 37 publications

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“…Reports of sex differences in human NKTs are inconsistent, and data from the Immunological Genome Project show only low levels of sex hormone receptor RNA in human NKTs (Table 1 ). Increased blood NKT cell numbers in women relative to men was reported in some studies ( 137 – 139 ). Sex differences in NKT cells in respiratory virus infection have not been reported, but in view of the above studies, analyses of possible sex disparate responses in NKT function in murine models of IAV or RSV may yield important insights.…”

Section: Innate Lymphocytesmentioning

confidence: 73%

Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

2018

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Sex differences in the incidence and severity of respiratory virus infection are widely documented in humans and murine models and correlate with sex biases in numbers and/or functional responses of innate immune cells in homeostasis and lung infection. Similarly, changes in sex hormone levels upon puberty, pregnancy, and menopause/aging are associated with qualitative and quantitative differences in innate immunity. Immune cells express receptors for estrogens (ERα and ERβ), androgens (AR), and progesterone (PR), and experimental manipulation of sex hormone levels or receptors has revealed that sex hormone receptor activity often underlies sex differences in immune cell numbers and/or functional responses in the respiratory tract. While elegant studies have defined mechanistic roles for sex hormones and receptors in innate immune cells, much remains to be learned about the cellular and molecular mechanisms of action of ER, PR, and AR in myeloid cells and innate lymphocytes to promote the initiation and resolution of antiviral immunity in the lung. Here, we review the literature on sex differences and sex hormone regulation in innate immune cells in the lung in homeostasis and upon respiratory virus infection.

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Section: Innate Lymphocytesmentioning

confidence: 73%

Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

2018

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“…Previously, higher CMV-specific IL-2 secretion has been reported in females [34]. Furthermore, Bernin et al reported that the NKT cell ligand α-Galactosylceramide induced higher production of intracellular IFN-γ, IL-4, IL-17, and TNF by CD4+ and CD4 CD8 double negative NKT cells in women [35]. Di Benedetto et al suggested that there is a sex-related difference in the immunological impact of CMV and reported that in females and males CMV-infection had a different effect on T-cell subpopulations [36].…”

Section: Discussionmentioning

confidence: 99%

The Cytomegalovirus-Specific IL-21 ELISpot Correlates with Allograft Function of Kidney Transplant Recipients

Lindemann

Korth

Sun

et al. 2018

IJMS

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In kidney transplant recipients, the cytomegalovirus (CMV) is frequently causing infection/reactivation and can trigger allograft rejection. To assess the risk of reactivation, the cellular immune response against CMV is increasingly assessed by cellular in vitro methods, such as the interferon (IFN)-γ ELISpot. In the current study we compared the IFN-γ ELISpot with our newly established CMV-specific ELISpot assays determining IL-17A, IL-21, IL-22, granzyme B, and perforin and correlated the results with flow cytometric data and clinical parameters. In 77 kidney transplant recipients, the highest frequency was observed for CMV pp65-specific cells secreting IFN-γ, followed by cells secreting IL-21 (62.9 and 23.2 Δ spot forming cells/105 cells). We observed a positive correlation between the percentage of CMV-specific CD3+ CD4+ CD154+ cells and results of the CMV-specific IL-21 ELISpot (p = 0.002). Results of the CMV pp65-specific IL-21 ELISpot correlated negatively with kidney function (estimated glomerular filtration rate, p = 0.006) and were significantly higher in women (p = 0.005). IL-21, a cytokine involved in aging that is secreted by activated CD4+ T cells, may also impact on allograft function. Thus, the CMV-specific IL-21 ELISpot could become a new tool to assess if CMV seropositivity represents a hazard for the graft.

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“…This antigen-specific cytotoxicity is CD95/CD95L dependent, unlike NK- and T cells that predominantly use perforin/granzyme-mediated mechanisms ( 115 ). Upon activation via their TCR in a CD1d-dependent manner, NKT cells rapidly expand and secrete a range of cytokines ( 68 , 116 – 120 ). Crowe et al reported ~10-fold expansion of type I NKT cell numbers in the murine spleen 2–3 days after injection with 2 µg α-GalCer in mice ( 116 ).…”

Section: Activation Of Nkt Cellsmentioning

confidence: 99%

The Role of Natural Killer T Cells in Cancer—A Phenotypical and Functional Approach

2018

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Natural killer T (NKT) cells are a subset of CD1d-restricted T cells at the interface between the innate and adaptive immune system. NKT cells can be subdivided into functional subsets that respond rapidly to a wide variety of glycolipids and stress-related proteins using T- or natural killer (NK) cell-like effector mechanisms. Because of their major modulating effects on immune responses via secretion of cytokines, NKT cells are also considered important players in tumor immunosurveillance. During early tumor development, T helper (TH)1-like NKT cell subsets have the potential to rapidly stimulate tumor-specific T cells and effector NK cells that can eliminate tumor cells. In case of tumor progression, NKT cells may become overstimulated and anergic leading to deletion of a part of the NKT cell population in patients via activation-induced cell death. In addition, the remaining NKT cells become hyporesponsive, or switch to immunosuppressive TH2-/T regulatory-like NKT cell subsets, thereby facilitating tumor progression and immune escape. In this review, we discuss this important role of NKT cells in tumor development and we conclude that there should be three important focuses of future research in cancer patients in relation with NKT cells: (1) expansion of the NKT cell population, (2) prevention and breaking of NKT cell anergy, and (3) skewing of NKT cells toward TH1-like subsets with antitumor activity.

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The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus

Cited by 38 publications

References 37 publications

Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

The Cytomegalovirus-Specific IL-21 ELISpot Correlates with Allograft Function of Kidney Transplant Recipients

The Role of Natural Killer T Cells in Cancer—A Phenotypical and Functional Approach

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