[Role of alloreactive natural killer cell in mouse MHC haploidentical bone marrow transplantation].
OBJECTIVE
To study the effect of alloreactive natural killer (NK) cells used in conditioning regimen on elimination of recipient-type T cell and granulocyte, reconstitution of hematopoiesis, engraftment and graft-versus-host disease (GVHD) in murine major histocompatibility complex (MHC) haploidentical bone marrow transplantation (BMT).


METHODS
The murine model of MHC haploidentical BMT was established by using (C57BL/6 x BALB/c) BCF(1) (H-2(d/b)) mouse as the donor, and BALB/c (H-2(d)) mouse as the recipient. Recipient mice were divided into 8.5 Gy control group and 7, 6 and 5 Gy experimental groups according to different irradiation dose and different kinds of NK cell treatment. The control group was further subdivided into untreated and BMT groups, while each experimental group was subdivided respectively into untreated group, BMT group, non-allo-reactive NK cells (non-allo NK) group and alloreactive NK cells (allo NK) group. The effect of adding alloreactive NK cell to conditioning regimen was assessed by peripheral white blood cell and platelet counts, recipient type H-2(d+) T cells and granulocytes counts, expression of H-2(d/b+) cells and pathohistological examination.


RESULTS
Survival time was (6.00 +/- 0.82) days for 8.5 Gy untreated group, and beyond 60 days for all the other groups. No clinical and histopathological evidence of GVHD was observed in all the groups. The reconstitution of hematopoiesis was faster in allo NK groups than in other groups (P < 0.05). On day 1 after BMT, in allo NK groups with different irradiation dose, bone marrow and spleen recipient type H-2(d+) granulocytes and T cells were significantly decreased compared with identical BMT groups and non-allo NK groups (P < 0.05). The engraftment rates of H-2(d/b+) cells were significantly higher in 7, 6 and 5 Gy allo NK groups than in identical BMT groups and non-allo NK groups (P < 0.05, respectively).


CONCLUSIONS
In mouse MHC haploidentical BMT, alloreactive NK cell can eliminate recipient-type T cell and granulocyte, promote reconstitution of hematopoiesis, enhance engraftment while not induce GVHD.
He
Yi
Y
Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020, China.
Wang
He-hua
HH
Wang
Mei
M
Zhou
Zheng
Z
Zhai
Wen-jing
WJ
Huang
Yong
Y
Jiang
Er-lie
EL
Wang
Zhi-dong
ZD
Zhou
Shi-yong
SY
Liu
Qing-guo
QG
Feng
Si-zhou
SZ
Han
Ming-zhe
MZ
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods