An investigation into the phenotype, function and immunomodulatory properties of in vitro expanded iNKT cells

Dempsey, Claire (2019). An investigation into the phenotype, function and immunomodulatory properties of in vitro expanded iNKT cells. University of Birmingham. Ph.D.

Preview

Dempsey19PhD.pdf
Text
Available under License All rights reserved.
Download (4MB) | Preview

Abstract

Invariant natural killer T (iNKT) cells are endowed with features of both innate and adaptive immunity. They are activated by the recognition of glycolipid agonists presented by CD1d which makes them excellent candidates for cellular therapies.

In order to investigate the ability of iNKT cells to suppress experimental acute Graft versus host disease (GVHD), iNKT cells were first expanded in vitro, which is likely to be required prior to their use as a cellular therapeutic. Interestingly, the expanded cells showed increased frequencies of IL-10, IL-13 and IL-17 producing cells and were found to robustly suppress alloreactive T cell proliferation in vitro compared to freshly isolated cells. However, in a model of acute GVHD induced by alloantigen-reactive TCR-transgenic T cells neither freshly isolated nor expanded iNKT cells suppressed GVHD, although some survival benefit was seen following the activation of host iNKT cells.

These data indicate that iNKT cells can be expanded ex vivo, that they can acquire different functional properties and that such cells robustly suppress alloreactive T cell proliferation in vitro. Therefore, further investigation into the suppressive behaviour of these cells is warranted despite a failure to suppress acute GVHD in the current study.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):