Effect of NK Cell on Gvhd in H-2 Haploidentical Bone Marrow Transplantation in Mice

Allogeneic haemopoietic stem-cell transplantation (HSCT) is a definitive cure for many malignant blood diseases. Ideal donors for transplantation are those with completely matched human leukocyte antigen (HLA), kin-relative or no-kin-relative. However only about 25% to 30% people could find HLA matched related-donor and there is only 1/100,000 opportunity to find a matched HLA in unrelated group. Recent years HLA haploidentical transplantation play more and more important role in across the histocompatibility barrier and make about 90% patients possible to get transplantation. However GVHD is still main problem during the transplantation. Recent studies show that natural killer (NK) cells could specially attack recipient antigen-presenting cells (APCs), shown to be responsible for decreasing and improving GVHD. To explore the effect of NK cell on GVHD after H-2 haploidentical bone marrow transplantation(BMT) in mice, we purified NK cells by positive selection with CD49b (DX5) MicroBeads (Miltenyi Biotec product) from donor mice as ingredient in the conditioning regimens, and observed the influence of donor NK cells on GVHD and evaluated the potential role of donor NK cells in protecting against GVHD. Murine model of H-2 haploidentical BMT was established by using Balb/c(H-2^d) mouse as recipient, and Balb/c (H-2^d)×C57BL/6 (H-2^b)(H-2^d/b) mouse as donor. Lethally irradiated Balb/c(H-2^d) mice were transplanted with Balb/c(H-2^d)×C57BL/6(H-2^b)(H-2^d/b) bone marrow containing donor peripheral T cells and/or NK cells. GVHD and survival rate were studied by observing clinical manifestations and pathological changes. In the group with bone marrow plus T cells, GVHD was induced in 90% mice; but in the group plus with low concentration of NK cells, GVHD was induced in 20% mice; and in the group transplanted with high concentration of NK cells, GVHD was induced only in 10% mice. Compared with the group transplanted only with T cells, the incidences of GVHD in the latter two groups decreased obviously (P<0.01) and the survival rate at 15, 30, 45 and 60 days increased obviously (P<0.01). In mouse H-2 haploidentical BMT, alloreactive NK cells can reduce the incidence of GVHD and increase the survival rate after transplantation in mice.