Author : Akshat Sharma
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (18 download)
Book Synopsis The Innate Effector Programmes of Invariant Natural Killer T-cells by : Akshat Sharma
Download or read book The Innate Effector Programmes of Invariant Natural Killer T-cells written by Akshat Sharma and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: T-cell effector functions exemplify adaptive immunity in that they 'adapt' to the threat at hand via a programme of antigen recognition, clonal expansion and subsequent contraction, and the generation of long-lived memory cells as insurance against subsequent insult. Invariant Natural Killer T (iNKT) cells are a lipid-reactive lineage of T-lymphocyte which, via an invariant T-cell receptor and epigentically 'poised effector' status, combine both the specificity of adaptive immunity as well as the rapid 'trained' responses of innate immunity. While a lot has been written about adaptive, antigen-specific or TCR-driven mechanisms of iNKT functionality, less is known about non-TCR or innate cues that drive iNKT responses. This disquisition aims to explore the same via enquiring after the functional consequences of having unusually high cell-surface expression of the integrin and co-stimulatory molecule Leucocyte Function-associated Antigen-1 (LFA-1) as well as the means by which iNKT cells serve as cellular adjuvants in a humanised mouse model of EBV-driven lymphomagenesis. For the former, we stimulated clonal or short-term polyclonal lines of human iNKT cells with plate-bound ICAM-1-Fc in the absence of antigen-presenting cells, but in the presence or absence of exogenous IL-12p70 to investigate the role that LFA-1:ICAM-1 interactions play in co-stimulating TCR-independent means of cell responsiveness. Surprisingly, we found that ICAM-1-fc alone is sufficient to drive IFNg from iNKT cells, and does not require concurrent TCR or pro-inflammatory cytokine cues. Immunotherapy work was performed within an in vivo model of EBV-driven lymphomagenesis using humanised mice. iNKT cells appear to promote tumour clearance via the activation of endogenous MHC-restricted T-cells. Whether or not the iNKT-TCR is involved in potentiating this programme of adjuvanticity will be a topic for future experiments. Ultimately, the work curated here builds a case for the versatility of iNKT cells via their ability to be sensitive to changes in their milieu that do not always involve direct antigen presentation. This ability to 'stay current' is what posits iNKT cells as a vital conduit, bridging the 'communication gaps' between classically innate and adaptive immune responses.