List of Titles

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

- Chan, Angela, Neeson, Paul, Leeansyah, Edwin, Tainton, K., Quach, Hang, Prince, Henry, Godfrey, Dale, Ritchie, David, Berzins, Stuart

Authors: Chan, Angela , Neeson, Paul , Leeansyah, Edwin , Tainton, K. , Quach, Hang , Prince, Henry , Godfrey, Dale , Ritchie, David , Berzins, Stuart
Date: 2010
Type: Text , Journal article
Relation: Leukemia Vol. 24, no. 3 (2010), p. 592-600
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Description: Myelodysplastic syndrome (MDS) comprises a group of clonal bone marrow disorders characterized by ineffective hematopoiesis and increased predisposition to acute myeloid leukemia. The causes of MDS remain poorly defined, but several studies have reported the NKT cell compartment of patients with MDS is deficient in number and functionally defective. In support of a central role for NKT cells, a pilot clinical study reported that lenalidomide (an approved treatment for MDS) increased NKT cell numbers in patients with MDS, and several in vitro studies showed lenalidomide specifically promoted NKT cell proliferation and cytokine production. We tested this in a much larger study and confirm a moderate in vitro augmentation of some NKT cell functions by lenalidomide, but find no impact on the NKT cell compartment of patients treated with lenalidomide, despite a consistently positive clinical response. We further show that the frequency and cytokine production of NKT cells is normal in patients with MDS before treatment and remains stable throughout 10 months of lenalidomide therapy. Collectively, our data challenge the concept that NKT cell defects contribute to the development of MDS, and show that a clinical response to lenalidomide is not dependent on modulation of NKT cell frequency or function. © 2010 Macmillan Publishers Limited All rights reserved.

Natural killer T cells: Drivers or passengers in preventing human disease?

- Berzins, Stuart, Richie, David

Authors: Berzins, Stuart , Richie, David
Date: 2014
Type: Text , Journal article
Relation: Nature Reviews Immunology Vol. 14, no. 9 (2014), p. 640-646
Full Text: false
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Description: Natural killer T (NKT) cells are credited with regulatory roles in immunity against cancers, autoimmune diseases, allergies, and bacterial and viral infections. Studies in mice and observational research in patient groups have suggested that NKT cell-based therapies could be used to prevent or treat these diseases, yet the translation into clinical settings has been disappointing. We support the view that NKT cells have regulatory characteristics that could be exploited in clinical settings, but there are doubts about the natural roles of NKT cells in vivo and whether NKT cell defects are fundamental drivers of disease in humans. In this Opinion article, we discuss the uncertainties and opportunities regarding NKT cells in humans, and the potential for NKT cells to be manipulated to prevent or treat disease. © 2014 Macmillan Publishers Limited.

Characterization of the localized immune response in the respiratory tract of ferrets following infection with influenza A and B viruses

- Carolan, Louise, Rockman, Steve, Borg, Kathryn, Guarnaccia, Teagan, Reading, Patrick, Mosse, Jennifer, Kelso, Anne, Barr, Ian, Laurie, Karen

Authors: Carolan, Louise , Rockman, Steve , Borg, Kathryn , Guarnaccia, Teagan , Reading, Patrick , Mosse, Jennifer , Kelso, Anne , Barr, Ian , Laurie, Karen
Date: 2016
Type: Text , Journal article
Relation: Journal of Virology Vol. 90, no. 6 (2016), p. 2838-2848
Full Text: false
Reviewed:
Description: The burden of infection with seasonal influenza viruses is significant. Each year is typically characterized by the dominance of one (sub)type or lineage of influenza A or B virus, respectively. The incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. To improve our understanding of the impacts of seasonal influenza viruses, we directly compared clinical symptoms, virus shedding, and expression of cytokines, chemokines, and immune mediators in the upper respiratory tract (URT) of ferrets infected with contemporary A(H1N1)pdm09, A(H3N2), or influenza B virus. Gene expression in the lower respiratory tract (LRT) was also assessed. Clinical symptoms were minimal. Overall cytokine/chemokine profiles in the URT were consistent in pattern and magnitude between animals infected with influenza A and B viruses, and peak expression levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p40, alpha interferon (IFN-α), IFN-β, and tumor necrosis factor alpha (TNF-α) mRNAs correlated with peak levels of viral shedding. MCP1 and IFN-γ were expressed after the virus peak. Granzymes A and B and IL-10 reached peak expression as the virus was cleared and seroconversion was detected. Cytokine/chemokine gene expression in the LRT following A(H1N1)pdm09 virus infection reflected the observations seen for the URT but was delayed 2 or 3 days, as was virus replication. These data indicate that disease severities and localized immune responses following infection with seasonal influenza A and B viruses are similar, suggesting that other factors are likely to modulate the incidence and impact of seasonal influenza. © 2016, American Society for Microbiology.

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