Essay about Natural Killer T ( Nkt ) Cells

Essay about Natural Killer T ( Nkt ) Cells

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- Recent intravital studies on natural killer T (NKT) cells have provided novel insights on the role of these cells during host defence77, 78 and immune-regulation79, 80. NKT cells share characteristics of both NK and T cells, and therefore act as a bridge between innate and adaptive immunity80, 81. Unlike conventional T cells that recognise peptide-MHC complexes, NKT cells recognise pathogen or self-derived glycolipids displayed on the major histocompatibility class I like protein, CD1d; and upon activation can release either TH1 or TH2 cytokines82-84. Although various subsets of NKT cells have recently been described85, Type I NKT (iNKT) cells are the most studied and are detailed in depth below.

In mice; liver by far contains the highest frequency of NKT cells and has been widely used to study NKT cell behaviour80. During homeostasis, NKT cells have been found to crawl actively within the liver sinusoids in a random manner77, 86. Surprisingly, crawling of NKT cells along sinusoidal endothelial cells was found to be independent of chemokine receptor, CXCR6 present on the NKT cells. However, CXCR6 mediated signalling was important for NKT cell survival86. Within the liver; hepatocytes, Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells were found to express CD1d86. Administration of surrogate NKT cell antigen α-galactosyl ceramide (α-GalCer) resulted in migratory arrest86 and initiation of NKT cell effector functions87, suggesting that the active crawling of NKT cells in the liver might act as an immunosurveillance mechanism. Other than α-GalCer, bacterial derivative galacturonic acid-containing glyco-sphingolipid (GalA-GSL) can induce CD1d dependent migratory arrest of NKT cells within the liver87. Similarl...

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...und to patrol surrounding tissue with similar dynamics to that observed for conventional T cells. Intravenous administration of particles coated with GalA‐GSL or α-GalCer resulted in the activation of NKT cells. Post-administration, the lipid-antigen was found to be present on marginal zone macrophages and CD11c+ DCs. Presence of antigen in the marginal zone resulted in decreased migratory speed and increased arrest of NKT cells in close proximity to the cells containing lipid-antigens88.

Taken together these studies highlight the unique role of lipid antigen-CD1d complexes, neurotransmitters and innate cytokines in altering NKT cell activation and migratory behaviour, resulting in alteration of immune responses. These studies further highlight the dynamic and organ specific behaviour of NKT cells in mediating immunity against various pathogens like B. burgdorferi.

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