PMID- 16969294 OWN - NLM STAT- MEDLINE DCOM- 20061025 LR - 20061115 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 82 IP - 5 DP - 2006 Sep 15 TI - Critical roles of memory T cells and antidonor immunoglobulin in rejection of allogeneic bone marrow cells in sensitized recipient mice. PG - 689-98 AB - BACKGROUND: Allosensitization is a major risk factor for graft failure in clinical bone marrow transplantation, even with an human leukocyte antigen (HLA)-matched combination under radiation-based conditioning regimens. The critical components of immunological memory in donor bone marrow graft rejection in allosensitized hosts remain unclear at present. METHODS: C57BL/6-recipient mice, which had been intraperitoneally injected with splenocytes from donor C3H mice on day -35 (sensitized recipients), had been lethally irradiated with 10-Gy whole-body irradiation and were intravenously injected with T-cell-depleted bone marrow cells (TCD-BMC) from C3H mice or third-party SJL mice. RESULTS: Lethally irradiated recipient mice, which had been sensitized by donor splenocytes 5 weeks before the transplantation of TCD-BMC, completely rejected the donor-BMC in a donor-specific manner, whereas none of the nonsensitized recipient mice, all of which showed full allogeneic chimerism, rejected the donor TCD-BMC. Antibody-mediated T cell and/or Natural Killer (NK) cell depletion did not improve the ability of the sensitized recipients to overcome the rejection even when a megadose of TCD-BMC was administered to the sensitized recipients. Furthermore, BMC rejection occurred in sensitized B cell-deficient mice. In adoptive transfer experiments, naive mice, which received a transfer of purified T cells from sensitized mice, rejected the donor BMC, but not those from nonsensitized mice. Moreover, naive mice, which received a transfer of serum containing antidonor immunoglobulin, rejected the donor BMC. CONCLUSIONS: These findings suggest that alloreactive memory T cells and antidonor immunoglobulin independently function to reject donor BMC in sensitized recipients. FAU - Nagata, Shigeyuki AU - Nagata S AD - Division of Pathophygiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Okano, Shinji AU - Okano S FAU - Yonemitsu, Yoshikazu AU - Yonemitsu Y FAU - Nakagawa, Kazunori AU - Nakagawa K FAU - Tomita, Yukihiro AU - Tomita Y FAU - Yoshikai, Yasunobu AU - Yoshikai Y FAU - Shimada, Mitsuo AU - Shimada M FAU - Maehara, Yoshihiko AU - Maehara Y FAU - Sueishi, Katsuo AU - Sueishi K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplantation JT - Transplantation JID - 0132144 SB - IM MH - Adoptive Transfer MH - Animals MH - Bone Marrow Transplantation/*immunology MH - Graft Rejection/*immunology MH - Immunization/*methods MH - *Immunologic Memory MH - Lymphocyte Transfusion MH - Mice MH - Models, Animal MH - T-Lymphocytes/*immunology/transplantation MH - Tissue Donors MH - Transplantation, Homologous/immunology EDAT- 2006/09/14 09:00 MHDA- 2006/10/26 09:00 CRDT- 2006/09/14 09:00 PHST- 2006/09/14 09:00 [pubmed] PHST- 2006/10/26 09:00 [medline] PHST- 2006/09/14 09:00 [entrez] AID - 00007890-200609150-00015 [pii] AID - 10.1097/01.tp.0000235589.66683.0e [doi] PST - ppublish SO - Transplantation. 2006 Sep 15;82(5):689-98. doi: 10.1097/01.tp.0000235589.66683.0e.