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Differential survival of γδT cells, αβT cells and NK cells upon engagement of NKG2D by NKG2DL-expressing leukemic cells.

Abstract：

:Herein, we show that γδT, CD8(+) αβT lymphocytes and natural killer (NK) cells display a different sensitivity to survival signals delivered via NKG2D surface receptor. All the three effector cell populations activate Akt1/PKBalpha through the engagement of this molecule. Upon binding to leukemic cells expressing NKG2D ligands (NKG2DL), including chronic lymphocytic leukemias treated with transretinoic acid, most γδT (>60%) and half CD8(+) αβT cells (about 50%) received a survival signal, at variance with the majority of NK cells (>80%) that underwent apoptosis by day 5. Interestingly, oligomerization of NKG2D in γδT or CD8(+) αβT cells, led to a significant rise in nuclear/cytoplasmic ratio of both NF-kBp52 and RelB, the two NF-kB subunits mainly involved in the transcription of antiapoptotic proteins of the Bcl family. Indeed, the ratio between the antiapoptotic protein Bcl-2 or Bcl-x(L) and the proapoptotic protein Bax raised in γδT or CD8(+) αβT cells following NKG2D engagement by specific monoclonal antibodies or by NKG2DL expressing leukemic cells. Conversely, nuclear translocation of NF-kBp52 or RelB did not increase, nor the Bcl-2/Bax or the Bcl-x(L) /Bax ratios changed significantly, in NK cells upon oligomerizaton of NKG2D. Of note, transcripts for α5 importin, responsible for nuclear translocation of NF-kBp52/Rel B heterodimer, are significantly higher in γδT and CD8(+) αβT cells than in NK cells. These biochemical data may explain, at least in part, why γδT and CD8(+) αβT cells are cytolytic effector cells more resistant to target-induced apoptosis than NK cells.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Poggi A,Zancolli M,Boero S,Catellani S,Musso A,Zocchi MR

doi

10.1002/ijc.25682

subject

Has Abstract

pub_date

2011-07-15 00:00:00

pages

387-96

issue

2

eissn

0020-7136

issn

1097-0215

journal_volume

129

pub_type

杂志文章

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