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In 2003, Parham and McQueen [1] stated a review that natural killer (NK) cell can not only strengthen graft versus leukaemia, but also inhibit graft rejection and graft versus host disease, boost the implantation of hematopoietic stem cells. Therefore, NK cell plays an important role in allogenic hematopoietic stem cell transplantation (allo-HSCT). Taking the allo-BMT in mice as experimental model, our team has already examined the role of NK cells in allo-HSCT and proved that NK cell can prevent graft versus host disease[2]. This article will further study the effect of NK cell on graft rejection, hematopoietic and immune reconstitution.

Recent research demonstrates that in haplotype-mismatched allo-HSCT, if recipients are short of one killer-cell immunoglobulin receptor (KIR) epitope on donor NK, that is, the KIR ligand incompatibility in the graft-versus-host direction, the MHC class Ⅰ specific inhibitory KIR cannot recognize the ligand and will hence intercept the inhibitory signal. On the other hand, other non-MHC class Ⅰ specific activating NKRs (such as NKG2D) can recognize ligand, and activate alloreaction to aim directly at recipients allogenic cells mediated by donor NK cells. Alloreaction may probably greatly affect the allo-HSCT outcome, such as graft versus leukaemia, graft versus host disease, graft rejection, implantation of stem cells, hematopoietic and immune reconstitution[1, 5-6].
The alloreaction of mice NK cell are regulated by the recognition between lectin-like receptors (Ly49 family) and its correspondent MHC class I molecule ligand. Similar to human KIR, the combination of the mice Ly49 receptor with the MHC class Ⅰ molecule ligand can inhibit the activity of NK cell[7-9]. The NK cell in H-2b mice mainly expresses Ly49C receptors, and the NK cell in H-2d mice expresses Ly49A receptor epitope. The Ly49A can recognize specifically the ligand of H-2d and cannot be combined with H-2b[10]. Our research is to experiment allo-BMT on H-2b and H-2d mice with mismatched Ly49 receptor epitope, study the effect of alloreactive NK cell on graft rejection and hematopoietic and immune reconstitution. The result proves that the allo-reactive NK cell promotes the engraftment of hematopoietic stem cells, and the reconstitution of hematopoiesis and immunity. Among long survival recipient mice in the lethal-dose TBI groups, the expression of H-2Kb+ cells over 80% on both the BM+NK cells and BM+T+NK cells groups; in contrast, the H-2Kb+ cells expression of the two long survival mice on Allo-BM group only comes to (4.68±0.32)%. Such result suggests that NK cells inhibit graft rejection and help to steady high level donor chimerism.
In the allo-BMT under the condition of non-lethal dose TBI, a further research into the effect of NK cell on graft rejection tells that the recipient mice reject the transplanted allogenic cells and survive long due to restoration of self hematopoiesis. The results further reveal that over 80% expression of H-2Kb+ cells are still with two groups of recipient mice with the infusion of both highly-condensed and lowly-condensed NK cells at 60 days after transplantation. Ruggeri et al[5] also discovered in their haplotype-mismatched BMT experiment with H-2d/b donors and H-2b/ H-2d recipients that, if injecting 2×105 alloreactive NK cells, even the recipients only receiving non-lethal dose TBI
(≤7 Gy), the possibility of donor chimerism goes to 80%. In this research and Ruggeri L’s transplantation model, incompatible NKR epitope in graft-versus-host direction exists and can activate allo-reaction to aim directly at recipients’ allogenic cells mediated by donor NK cells. Furthermore, the similar result from 2 different transplantation models attests that alloreactive NK cell can inhibit graft rejection and improve the implantation of stem cells. These function of NK cell in allo-BMT is probably caused by the NK cell alloreaction which can attacks the recipients T cells, that is immune functionary cells of graft rejection, and suggests that alloreactive NK cell can partially substitute for function to restrict the recipient immunity in place of TBI.
It is noticeable that, alloreactive NK cells would benefit to restore the immune function of B cell. The expression of CD3+ cell in both allo-BM and BM+T cell groups increased gradually after transplantation, while it decreased before the increase on the two groups with the infusion of NK cells. Whether the phenomenon is related to the clearance of recipients T cells due to the effect of NK cell’s alloreaction, it is yet to be answered because of the deficiency of the evaluation index in absolute count. In any case, the experimental result suggests that the alloreactive NK cell can inhibit graft rejection, improve the implantation of hematopoietic stem cells and advance hematopoietic and immune reconstitution.

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