Rapid NKG2D Reconstitution on NK Cells Possibly Plays a Major Role in the Development of Graft-Versus-Leukemia Effect in the Early Period after Unrelated Cord Blood Transplantation.

Background: Cord blood transplantation (CBT) is being increasingly used for treatment of hematologic malignancies due to its potent anti-leukemic effects and the low incidence of graft-versus-host disease (GVHD). Recent study has shown that recovery of natural killer (NK) cells is prompt in the blood of CBT recipients both in numbers and functions during the first two months, suggesting that NK cells play an important role in the GVL effect in CBT. NKG2D is an activating receptor expressed by NK cells, which recognizes human MHC class I chain related A and B (MICA/B) and UL16-binding protein 1–4 (ULBP1-4) on target cells, and regulates NK cell activity. However, NKG2D reconstitution following CBT is presently unclear. In this study, we investigated the dynamic expression of NKG2D and other receptors on CD3⁻CD56⁺ NK cells in the early period after CBT.

Material and methods: The study panel comprised 21 leukemia patients receiving allogeneic hematopoietic cell transplants. Of these, 10 received unrelated CBT and 11 received allogeneic transplants with peripheral blood (PB) combined with bone marrow (BM). To examine the recovery of NKG2D, and other receptors expressed by NK cells, flow cytometry was used to evaluate samples obtained from the recipients on day of clinical engraftment, 30, 60, and 90, respectively following transplantation.

Results: Recovery of NK cells was prompt in both transplantation groups (CBT and PB combining with BM), which is consistent with the previous reports. Interestingly, there are significant differences in NKG2D reconstitution between CBT and PB combining with BM transplantation in early stage after transplantation. CBT recipients showed significantly increased expression of NKG2D compared to PB combining with BM transplantation recipients on day of clinical engraftment (79.58±8.71 VS 36.7±14.33 P<0.03 ) and day 30 after transplantation ( 80.03±13.49 VS 56.8±18.21 p<0.035 ). However there was no differences for NKG2D expression between the CBT and PB combined with BM transplantation groups on day 60(82.55±9.10 VS 82.3±28.64 p<0.01 )and on day 90 (85.82±18.21 VS 90.3±27.89 p<0.01), respectively. The inhibitory NK receptor NKG2A reconstitution occurred at the early period, and the expression was not significantly changed during the first three months in CBT, although the level was lower than the other transplantation group. The reconstitution of other inhibitory NK receptors (CD94, CD158a and CD158b) and activating receptor (NKp46) was not found statistically significant differences between the two transplantation groups. T and B cells reconstitution started gradually, and remained at low level at the end of investigation period in CBT recipients.

Conclusion: NK cells contribute to GVL effects after transplantation maybe due to rapid NKG2D reconstitution. Rapid NKG2D reconstitution on NK cells in CBT recipients than blood combined bone marrow transplantation suggests that CBT appears superior to blood combined bone marrow transplantation in the treatment of leukemia patients.