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Novel pathway of thymus-dependent NK...

Veinotte, Linnea Lora.

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Novel pathway of thymus-dependent NK cell development.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Novel pathway of thymus-dependent NK cell development./
Author:	Veinotte, Linnea Lora.
Description:	122 p.
Notes:	Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2055.
Contained By:	Dissertation Abstracts International68-04B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR26817
ISBN:	9780494268179

Novel pathway of thymus-dependent NK cell development.
Veinotte, Linnea Lora.

Novel pathway of thymus-dependent NK cell development. - 122 p.

Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2055.

Thesis (Ph.D.)--The University of British Columbia (Canada), 2007.

Natural killer (NK) cells are the major lymphocytes of the innate immune system, but their developmental pathway is not fully defined. It is commonly assumed that all NK cells develop in the bone marrow. In this thesis, I describe a novel thymus-dependent pathway of NK cell development that is specific to those in the thymus and lymph nodes. Microarray analysis revealed TCRgamma mRNA expression in NK cells. Genomic and RT-PCR showed that some NK cells have rearranged TCRgamma genes while TCRbeta and TCRdelta genes are in germline order. NK cells with rearranged TCRgamma (Tcrgamma + NK cells) were absent in nude mice indicating that they are thymus-dependent. Approximately half of thymus NK cells have rearranged TCRgamma genes and in vitro cultures of immature thymocytes (double negative (DN)1 and DN2 progenitors) produced Tcrgamma+ NK cells, strongly suggesting that these are the thymus-dependent NK cell progenitors in vivo. Thymus NK cells are CD94/NKG2hi Ly49 lo Mac-1lo IL-7Ralphahi and they have normal cytotoxicity levels but reduced IFNgamma production. By using TCRgamma gene rearrangement as a marker of thymus-dependent NK cells, we showed that they are also present in lymph nodes (LNs) but in no other tissues tested. NK progenitors similar to immature thymocytes were found in LNs and LN Tcrgamma+ NK cells and LN progenitors were also absent in nude mice. In vitro cultures and preliminary in vivo studies suggest that the NK progenitors in the LN give rise to mature NK cells. The results suggest that immature thymocytes migrate to LNs and differentiate into NK cells. It is likely that the thymus-dependent NK cells play a special role in the immune response since their phenotype is unique. Finally, this study suggests that multiple pathways of NK cell commitment exist in multiple tissues. The differences in tissue environment may influence the phenotype and function of NK cells, resulting in multiple subsets of NK cells throughout the body.

ISBN: 9780494268179Subjects--Topical Terms:

1017730
Biology, Genetics.

Novel pathway of thymus-dependent NK cell development.
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100 1 $a Veinotte, Linnea Lora. $3 1267706
245 1 0 $a Novel pathway of thymus-dependent NK cell development.
300 $a 122 p.
500 $a Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2055.
502 $a Thesis (Ph.D.)--The University of British Columbia (Canada), 2007.
520 $a Natural killer (NK) cells are the major lymphocytes of the innate immune system, but their developmental pathway is not fully defined. It is commonly assumed that all NK cells develop in the bone marrow. In this thesis, I describe a novel thymus-dependent pathway of NK cell development that is specific to those in the thymus and lymph nodes. Microarray analysis revealed TCRgamma mRNA expression in NK cells. Genomic and RT-PCR showed that some NK cells have rearranged TCRgamma genes while TCRbeta and TCRdelta genes are in germline order. NK cells with rearranged TCRgamma (Tcrgamma + NK cells) were absent in nude mice indicating that they are thymus-dependent. Approximately half of thymus NK cells have rearranged TCRgamma genes and in vitro cultures of immature thymocytes (double negative (DN)1 and DN2 progenitors) produced Tcrgamma+ NK cells, strongly suggesting that these are the thymus-dependent NK cell progenitors in vivo. Thymus NK cells are CD94/NKG2hi Ly49 lo Mac-1lo IL-7Ralphahi and they have normal cytotoxicity levels but reduced IFNgamma production. By using TCRgamma gene rearrangement as a marker of thymus-dependent NK cells, we showed that they are also present in lymph nodes (LNs) but in no other tissues tested. NK progenitors similar to immature thymocytes were found in LNs and LN Tcrgamma+ NK cells and LN progenitors were also absent in nude mice. In vitro cultures and preliminary in vivo studies suggest that the NK progenitors in the LN give rise to mature NK cells. The results suggest that immature thymocytes migrate to LNs and differentiate into NK cells. It is likely that the thymus-dependent NK cells play a special role in the immune response since their phenotype is unique. Finally, this study suggests that multiple pathways of NK cell commitment exist in multiple tissues. The differences in tissue environment may influence the phenotype and function of NK cells, resulting in multiple subsets of NK cells throughout the body.
590 $a School code: 2500.
650 4 $a Biology, Genetics. $3 1017730
690 $a 0369
710 2 $a The University of British Columbia (Canada). $3 626643
773 0 $t Dissertation Abstracts International $g 68-04B.
790 $a 2500
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR26817