PMID- 18307515 OWN - NLM STAT- MEDLINE DCOM- 20080512 LR - 20211020 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 152 IP - 1 DP - 2008 Apr TI - Prevention of graft-versus-host disease by intrabone marrow injection of donor T cells: involvement of bone marrow stromal cells. PG - 153-62 LID - 10.1111/j.1365-2249.2008.03615.x [doi] AB - We have developed a new and effective method for bone marrow transplantation (BMT): bone marrow cells (BMCs) are injected directly into the bone marrow (BM) cavity of recipient mice. The intrabone marrow injection of BMCs (IBM-BMT) greatly facilitates the engraftment of donor-derived cells, and IBM-BMT can attenuate graft-versus-host reaction (GVHR), in contrast to conventional intravenous BMT (i.v.-BMT). Here, we examine the mechanisms underlying the inhibitory effects of IBM-BMT on GVHR using animal models where GVHR is elicited. Recipient mice (C57BL/6) were irradiated and splenic T cells (as donor lymphocyte infusion: DLI) from major histocompatibility complex-disparate donors (BALB/c) were injected directly into the BM cavity (IBM-DLI) or injected intravenously (i.v.-DLI) along with IBM-BMT. The BM stromal cells (BMSCs) from these recipients were collected and related cytokines were examined. The recipient mice that had been treated with IBM-BMT + i.v.-DLI showed severe graft-versus-host disease (GVHD), in contrast to those treated with IBM-BMT + IBM-DLI. The suppressive activity of BMSCs in this GVHD model was determined. The cultured BMSCs from the recipients treated with IBM-BMT + IBM-DLI suppressed the proliferation of responder T cells remarkably when compared with those from the recipients of IBM-BMT + i.v.-DLI in mixed leucocyte reaction. Furthermore, the level of transforming growth factor-beta and hepatocyte growth factor in cultured BMSCs from IBM-BMT + IBM-DLI increased significantly when compared with those from the recipients of IBM-BMT + i.v.-DLI. Thus, the prevention of GVHD observed in the recipients of IBM-BMT + IBM-DLI was attributable to the increased production of immunosuppressive cytokines from BMSCs after interaction with host reactive T cells (in DLI). FAU - Miyake, T AU - Miyake T AD - First Department of Pathology, and Department of Surgery, Kansai Medical University, Osaka, Japan. FAU - Inaba, M AU - Inaba M FAU - Fukui, J AU - Fukui J FAU - Ueda, Y AU - Ueda Y FAU - Hosaka, N AU - Hosaka N FAU - Kamiyama, Y AU - Kamiyama Y FAU - Ikehara, S AU - Ikehara S LA - eng PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080225 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Interleukin-3) RN - 0 (Transforming Growth Factor beta) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Bone Marrow Cells/immunology MH - Bone Marrow Transplantation/*methods MH - Cell Proliferation MH - Cells, Cultured MH - Coculture Techniques MH - Graft vs Host Disease/immunology/*prevention & control MH - Hepatocyte Growth Factor/biosynthesis MH - Immune Tolerance MH - Interferon-gamma/biosynthesis MH - Interleukin-3/biosynthesis MH - Lymphocyte Transfusion/*methods MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Stromal Cells/*immunology MH - T-Lymphocyte Subsets/immunology/transplantation MH - Transforming Growth Factor beta/biosynthesis PMC - PMC2384073 EDAT- 2008/03/01 09:00 MHDA- 2008/05/13 09:00 PMCR- 2009/04/01 CRDT- 2008/03/01 09:00 PHST- 2008/03/01 09:00 [pubmed] PHST- 2008/05/13 09:00 [medline] PHST- 2008/03/01 09:00 [entrez] PHST- 2009/04/01 00:00 [pmc-release] AID - CEI3615 [pii] AID - 10.1111/j.1365-2249.2008.03615.x [doi] PST - ppublish SO - Clin Exp Immunol. 2008 Apr;152(1):153-62. doi: 10.1111/j.1365-2249.2008.03615.x. Epub 2008 Feb 25.