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.