Herein, we show that λδT, CD8 +λβT 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 λδT (>60%) and half CD8 +λβT 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 cdT or CD81abT 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-xL and the proapoptotic protein Bax raised in cdT or CD8 +λβT 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-xL/Bax ratios changed significantly, in NK cells upon oligomerizaton of NKG2D. Of note, transcripts for a5 importin, responsible for nuclear translocation of NF-kBp52/Rel B heterodimer, are significantly higher in λδT and CD8 +λβT cells than in NK cells. These biochemical data may explain, at least in part, why cdT and CD8 +λβT cells are cytolytic effector cells more resistant to target-induced apoptosis than NK cells.
ASJC Scopus subject areas
- Cancer Research