Unraveling Natural Killer T-Cells Development

Bennstein, Sabrina Bianca

doi:10.3389/fimmu.2017.01950

Cited by 50 publications

(40 citation statements)

References 59 publications

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“…However, whether the classic developmental stages model or the newer lineage segregation model best describes iNKT cell development, remains uncertain. Moreover, the specific signals required for commitment to the different iNKT cell subsets are largely unknown, although a multitude of factors, including cytokines and transcriptional regulators, can differentially regulate NKT1, NKT2, and NKT17 development ( 148 ). It would be worth investigating whether similar factors also modulate the differentiation of thymic MAIT cell subsets.…”

Section: Developmentmentioning

confidence: 99%

Insights Into Mucosal-Associated Invariant T Cell Biology From Studies of Invariant Natural Killer T Cells

2018

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Mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cells are innate-like T cells that function at the interface between innate and adaptive immunity. They express semi-invariant T cell receptors (TCRs) and recognize unconventional non-peptide ligands bound to the MHC Class I-like molecules MR1 and CD1d, respectively. MAIT cells and iNKT cells exhibit an effector-memory phenotype and are enriched within the liver and at mucosal sites. In humans, MAIT cell frequencies dwarf those of iNKT cells, while in laboratory mouse strains the opposite is true. Upon activation via TCR- or cytokine-dependent pathways, MAIT cells and iNKT cells rapidly produce cytokines and show direct cytotoxic activity. Consequently, they are essential for effective immunity, and alterations in their frequency and function are associated with numerous infectious, inflammatory, and malignant diseases. Due to their abundance in mice and the earlier development of reagents, iNKT cells have been more extensively studied than MAIT cells. This has led to the routine use of iNKT cells as a reference population for the study of MAIT cells, and such an approach has proven very fruitful. However, MAIT cells and iNKT cells show important phenotypic, functional, and developmental differences that are often overlooked. With the recent availability of new tools, most importantly MR1 tetramers, it is now possible to directly study MAIT cells to understand their biology. Therefore, it is timely to compare the phenotype, development, and function of MAIT cells and iNKT cells. In this review, we highlight key areas where MAIT cells show similarity or difference to iNKT cells. In addition, we discuss important avenues for future research within the MAIT cell field, especially where comparison to iNKT cells has proven less informative.

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Section: Developmentmentioning

confidence: 99%

Insights Into Mucosal-Associated Invariant T Cell Biology From Studies of Invariant Natural Killer T Cells

2018

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“…Recognition of CD1d-loaded endogenous lipid antigen(s) on CD4/CD8-double-positive (DP) thymocytes with interactions between signaling lymphocyte activation molecule (SLAM) family members is essential for the development of iNKT cells. After differentiating into different iNKT cell subsets in the thymus, these cells then distribute in peripheral organs ( 30 ). The role of SLAM signaling on changes in cytokine levels at different time points after KRN treatment needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Activation of Invariant Natural Killer T Cells Redirects the Inflammatory Response in Neonatal Sepsis

et al. 2018

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Sepsis is the third leading cause of death in the neonatal population, due to susceptibility to infection conferred by immaturity of both the innate and adaptive components of the immune system. Invariant natural killer T (iNKT) cells are specialized adaptive immune cells that possess important innate-like characteristics and have not yet been well-studied in septic neonates. We hypothesized that iNKT cells would play an important role in mediating the neonatal immune response to sepsis. To study this, we subjected 5- to 7-day-old neonatal C57BL/6 mice to sepsis by intraperitoneal (i.p.) cecal slurry (CS) injection. Thirty hours prior to or immediately following sepsis induction, pups received i.p. injection of the iNKT stimulator KRN7000 (KRN, 0.2 µg/g) or vehicle. Ten hours after CS injection, blood and tissues were collected for various analyses. Thirty-hour pretreatment with KRN resulted in better outcomes in inflammation, lung injury, and survival, while immediate treatment with KRN resulted in worse outcomes compared to vehicle treatment. We further analyzed the activation status of neonatal iNKT cells for 30 h after KRN administration, and showed a peak in frequency of CD69 expression on iNKT cells and serum IFN-γ levels at 5 and 10 h, respectively. We then used CD1d knockout neonatal mice to demonstrate that KRN acts through the major histocompatibility complex-like molecule CD1d to improve outcomes in neonatal sepsis. Finally, we identified that KRN pretreatment exerts its protective effect by increasing systemic levels of TGF-β1. These findings support the importance of iNKT cells for prophylactic immunomodulation in neonates susceptible to sepsis.

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“…NKT cells are subcategorized as NKT 1 , NKT 2 , NKT 17 and NKT FH dependent on their ability to match the cytokine profile of the representative Th line. (51) NKT cells are also a source of BAFF and APRIL, which are important survival factors for LLPC; (25,26) the presence of CD38 + mature plasma cells in biopsy cores from the CMJAH cohort may be further evidence for NKT in the interstitial infiltrate ( Figure 5).…”

Section: Therapeutic Failures Provide New Insights Into the Immunobiomentioning

confidence: 99%

Murder in the Cathedral: Antibodies and the Limits of Transplantation

Davies¹

2019

Wits Journal of Clinical Medicine

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Although transplantation is the optimal therapy for end-stage renal disease, long-term survival of kidney allografts remains elusive. Antibody-mediated rejection has been implicated as a major factor in late period graft loss. The refractory nature of late period antibody-mediated rejection is the evidence of an important immunological process with implications for other solid organ transplants and for other diseases. This review details advances in the understanding of late period antibody-mediated rejection in the context of local experience.

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Unraveling Natural Killer T-Cells Development

Cited by 50 publications

References 59 publications

Insights Into Mucosal-Associated Invariant T Cell Biology From Studies of Invariant Natural Killer T Cells

Insights Into Mucosal-Associated Invariant T Cell Biology From Studies of Invariant Natural Killer T Cells

Activation of Invariant Natural Killer T Cells Redirects the Inflammatory Response in Neonatal Sepsis

Murder in the Cathedral: Antibodies and the Limits of Transplantation

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