PMID- 19112915 OWN - NLM STAT- MEDLINE DCOM- 20100408 LR - 20081230 IS - 0253-2727 (Print) IS - 0253-2727 (Linking) VI - 29 IP - 8 DP - 2008 Aug TI - [Experimental study on IL-2- and IL-15 application in allogeneic hematopoietic stem cell transplantation]. PG - 526-30 AB - OBJECTIVE: To explore the impact of IL-2- and IL-15-activated donor natural killer (NK) cell infusion on graft-versus-host-disease (GVHD) and graft-versus-leukemia (GVL) effect post allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The C57BL/6 mice splenic NK cells were selected by microbeads, and then expanded in the media containing IL-2 and IL-15. The killing activity of NK cells was detected. In the leukemia mouse model, recipients (BALB/c) were intravenously inoculated with EL9611 leukemia cells 8 days before transplantation. Lethally irradiated BALB/c recipient mice were transplanted with 5 x 10(6) bone marrow cells (BMCs), or 5 x 10(6) BMCs plus 1 x 10(7) splenocytes with or without 1 x 10(7) activated NK cells. Additionally, NK cell infusion group mice were intraperitoneally injected with a mixture of IL-2 and IL-15 post transplant. Survival time, GVHD occurrence, lineage chimerism, TRBV spectra-typing were observed post transplant. RESULTS: The purity of isolated splenic NK cells was 95.7% - 97.1%. The killing activity of NK cells after activation was increased by 3 times. GVHD did not occurred in allogeneic BMCs infusion group, whereas did from 1 week after transplant in allogeneic BMCs + splenocytes infusion group. The severity of GVHD in total body irradiation (TBI) experimental group was significantly lower than in splenocytes infusion group (P < 0.05). The survival time was 9.5 - 14.0 d in TBI alone conditioning group. In leukemia mouse model, 100 day survival rate was 10% the rest of them were died of leukemia while in experimental group, the more than 100 days survival rate was 80% (P < 0.01). PB NK cells at 2 week post-transplant were 4.8% in experimental group and 2.8% in control group. NK cells recovery in experimental group was earlier than that in control group (P < 0.05). TRBV reconstitution was faster in experimental group than in control group, moreover, the number of TRBV family expression was more in experimental group than in control group which mainly expressed monoclone or oligo-clone. CONCLUSIONS: Donor alloreactive NK cells can be efficiently expanded and activated with IL-2 and IL-15. Donor activated NK cell infusion and IL-2, IL-15 treatment can promote immune reconstitution, mitigate GVHD and reduce leukemia relapse. FAU - Chen, Guang-Hua AU - Chen GH AD - Jiangsu Institute of Hematology, First Hospital of Soochow University, Suzhou 215006, China. FAU - Wu, De-Pei AU - Wu DP FAU - Sun, Ai-Ning AU - Sun AN FAU - Yang, Ming-Zhen AU - Yang MZ FAU - Wang, Yi AU - Wang Y FAU - Tang, Xiao-Wen AU - Tang XW FAU - Chang, Hui-Rong AU - Chang HR FAU - Feng, Yu-Feng AU - Feng YF FAU - Zhu, Zi-Ling AU - Zhu ZL LA - chi PT - English Abstract PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Zhonghua Xue Ye Xue Za Zhi JT - Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi JID - 8212398 RN - 0 (Interleukin-15) RN - 0 (Interleukin-2) SB - IM MH - Animals MH - Cells, Cultured MH - Graft vs Host Disease/prevention & control MH - Graft vs Leukemia Effect MH - *Hematopoietic Stem Cell Transplantation MH - Interleukin-15/*immunology/pharmacology MH - Interleukin-2/*immunology/pharmacology MH - Killer Cells, Natural/cytology/*immunology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL EDAT- 2008/12/31 09:00 MHDA- 2010/04/09 06:00 CRDT- 2008/12/31 09:00 PHST- 2008/12/31 09:00 [entrez] PHST- 2008/12/31 09:00 [pubmed] PHST- 2010/04/09 06:00 [medline] PST - ppublish SO - Zhonghua Xue Ye Xue Za Zhi. 2008 Aug;29(8):526-30.