Critical roles of memory T cells and antidonor immunoglobulin in rejection of allogeneic bone marrow cells in sensitized recipient mice
Critical roles of memory T cells and antidonor immunoglobulin in rejection of allogeneic bone marrow cells in sensitized recipient mice
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DOI：
10.1097/01.tp.0000235589.66683.0e
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发表时间：
2006-09-15
期刊：
影响因子：
6.2
通讯作者：
Sueishi, Katsuo
中科院分区：
文献类型：
--
作者：
Nagata, Shigeyuki;Okano, Shinji;Sueishi, Katsuo
背景。同种异体敏化是临床骨髓移植中移植物失败的主要危险因素，即使在放射治疗方案下使用人类白细胞抗原（HLA）匹配的组合也是如此。同种异体致敏宿主供体骨髓移植排斥反应中免疫记忆的关键成分目前尚不清楚。C57BL/6受体小鼠于第35天腹腔注射供体C3H小鼠的脾细胞（致敏受体），接受10 gy全身致死照射，并静脉注射C3H小鼠或第三方SJL小鼠的t细胞枯竭骨髓细胞（TCD-BMC）。在TCD-BMC移植前5周被供体脾细胞致敏的致毒受体小鼠，完全以供体特异性方式排斥供体- bmc，而未致敏的受体小鼠，均表现出完全的异体嵌合，均不排斥供体TCD-BMC。抗体介导的T细胞和/或自然杀伤（NK）细胞耗竭并没有提高致敏受体克服排斥反应的能力，即使给致敏受体注射大剂量的TCD-BMC。此外，BMC排斥发生在致敏的B细胞缺陷小鼠中。在过继性转移实验中，接受致敏小鼠的纯化T细胞转移的幼稚小鼠会排斥供体BMQ，而非致敏小鼠的供体BMQ则不会。此外，接受含有抗供体免疫球蛋白的血清转移的幼稚小鼠对供体bmc有排斥反应。这些发现表明，同种反应性记忆T细胞和抗供体免疫球蛋白在致敏受体中独立起排斥供体BMC的作用。
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 BMQ 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.