Tumor cells are able to induce activation in NK cells, represented by cytotoxicity and cytokine production. Recent studies suggest that the induction of these two functions of the NK cells have different requirements. This study investigates the hypothesis that the ability of tumor cells to induce cytokine production and/or cytotoxicity in NK cells depends on the expression of particular combinations of receptors on NK cells and ligands on the tumor cells.
Resting NK cells from five healthy donors, with distinct NK receptor repertoires, were activated by tumor cell lines and their ability to kill the tumor cells and to secrete IFNγ was evaluated. The tumor cell lines, represented by four myeloma cell lines and Daudi, K562 and Jurkat, were evaluated for their expression of several NK receptor activating ligands, (ULBPs, MICA/B, PRR2, CD48, HLA-E and HLA-G) inhibitory ligands, (MHC class I molecules), and adhesion molecules, (CD54, CD58, CD56 and CD45). Each tumor cell line expressed a particular combination of these ligands. Resting NK cells cocultured with the tumor cell lines were activated, thus able to kill the tumor cells and/or to secrete IFNγ. The induction of IFNγ-secreting NK cells in the resting NK population after exposure to tumor cell lines was positively correlated with the expression of the activating ligands ULBPs, PRR2, HLA-E and HLA-G and negatively correlated with the presence of HLA-C2 molecules. The coexpression of CD58 and CD54 along with ULBPs was suggested to be involved in induction of IFNγ secretion in resting NK cells. Resting NK cells were also able to kill the tumor cells, including the myeloma cell lines, through NKG2D-MICA/B interaction and Fas/FasL pathways. The coexpression of CD45 along with MICA/B had a positive effect on cytotoxicity, but CD56 was a negative regulator of tumor cell lysis.
In conclusion, the results suggest that the initiation of the two main functions of NK cells might be a result the interaction of distinct combinations of NK receptors and ligands and adhesion molecules expressed by tumor cells.
|Commitee:||Fulton, Amy, Moudgil, Kamal, Ostrand-Rosenberg, Suzanne, Stamatos, Nicholas|
|School:||University of Maryland, Baltimore|
|School Location:||United States -- Maryland|
|Source:||DAI-B 69/04, Dissertation Abstracts International|
|Subjects:||Cellular biology, Pathology, Immunology|
|Keywords:||Adhesion molecules, Cytotoxicity, NK cells, NK receptors|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be