PMID- 12182463 OWN - NLM STAT- MEDLINE DCOM- 20030312 LR - 20191106 IS - 0966-3274 (Print) IS - 0966-3274 (Linking) VI - 10 IP - 1 DP - 2002 Jun TI - Efficacy of donor splenocytes mixed with bone marrow cells for induction of tolerance in sublethally irradiated mice. PG - 37-41 AB - BACKGROUND: High dose of bone marrow cells (BMCs) has been reported to be essential to establish donor-specific tolerance. In clinical settings, a large quantity of BMCs is very difficult to be obtained. Our previous report demonstrated that even a low dose of BMCs could establish donor-specific tolerance if mixed with splenocytes (SPLCs). In the present study, various components of SPLCs were purified or removed and were investigated their contribution for enhancement of bone marrow engraftment leading to donor-specific tolerance in sublethally irradiated mice. METHODS: Sublethally irradiated C57BL/6 recipient mice were intravenously injected 3 x 10(6) BMCs mixed with various components and various numbers of SPLCs harvested from BALB/c donor mice. One week after injection, skin grafting was performed. The degree of chimerism in peripheral blood lymphocytes (PBLs) and in SPLCs was analyzed by FACS 3 months after transplantation. RESULTS: Recipients receiving 3 X 106 BMCs mixed with 10 x 10(6) T cell-enriched SPLCs established chimerism. Recipients receiving BMCs mixed with macrophage-depleted SPLCs also showed chimeirism and donor-specific tolerance. B cell-enriched SPLCs did not help small dose of BMCs to establish chimerism. Irradiated SPLCs were not effective to induce tolerance even with additional infusion to recipients. CONCLUSIONS: Active effects of splenic T cells were more important to help engraftment of small dose of BMCs than B cells, but the interaction between T and B cells might play some roles to enhance BMC engraftment. Splenic macrophages or dendritic cells might have some adverse effects against tolerance induction. Fatal graft-versus-host disease (GVHD) might be avoided by depleting adherent cells from SPLCs, so macrophages or dendritic cells were also considered as key components to induce donor-specific tolerance and prevent GVHD in this model. FAU - Hashimoto, Naoki AU - Hashimoto N AD - Second Department of Surgery, Hirosaki University School of Medicine, Japan. hashimo2@cc.hirosaki-u.ac.jp FAU - Narumi, Shunji AU - Narumi S FAU - Itabashi, Yukihiro AU - Itabashi Y FAU - Hakamada, Kenichi AU - Hakamada K FAU - Sasaki, Mutsuo AU - Sasaki M LA - eng PT - Journal Article PL - Netherlands TA - Transpl Immunol JT - Transplant immunology JID - 9309923 SB - IM MH - Animals MH - Bone Marrow Cells/physiology MH - *Bone Marrow Transplantation MH - Graft vs Host Disease/prevention & control MH - *Immune Tolerance MH - Mice MH - Mice, Inbred Strains MH - Skin Transplantation/immunology MH - Spleen/*cytology MH - Transplantation Chimera MH - Whole-Body Irradiation EDAT- 2002/08/17 10:00 MHDA- 2003/03/13 04:00 CRDT- 2002/08/17 10:00 PHST- 2002/08/17 10:00 [pubmed] PHST- 2003/03/13 04:00 [medline] PHST- 2002/08/17 10:00 [entrez] AID - S0966-3274(02)00020-5 [pii] AID - 10.1016/s0966-3274(02)00020-5 [doi] PST - ppublish SO - Transpl Immunol. 2002 Jun;10(1):37-41. doi: 10.1016/s0966-3274(02)00020-5.