Sca-1~+造血干/祖细胞重建致死剂量辐射小鼠造血功能的作用

背景:近年来,造血干细胞移植在国内外已广泛开展,移植的造血干细胞能否有效重建造血成为造血干细胞移植领域的研究热点问题之一。目的:观察Sca-1+造血干/祖细胞(hematopoietic stem/progenitor cell,Sca-1+HSC/HPC)对造血衰竭小鼠造血功能重建的作用。方法:雌性C57BL/6受体鼠给予致死剂量60Coγ射线照射后分2组,对照组:输注无菌PBS;移植组:移植免疫磁性分选法分离纯化的同系雄性C57BL/6小鼠Sca-1+HSC/HPC;检测受体鼠生存时间;外周血白细胞、红细胞比容、血小板的变化;脾湿质量及脾集落数;PCR检测Y染色体(Sry基因)表达确定受体小鼠重建造血的细胞来源。结果与结论:移植组受体鼠30d存活率、白细胞、红细胞比容、血小板、脾湿质量及脾集落数均明显高于对照组(P0.05);Y染色体PCR分析,证实雌性受体小鼠重建造血的细胞来源于雄性供体。提示Sca-1+HSC/HPC移植后能重建造血衰竭小鼠造血功能。     

混合骨髓移植后过继免疫治疗小鼠白血病

背景：急性白血病自体造血干细胞移植后复发率高,异基因造血干细胞移植后移植相关病死率高,混合造血干细胞移植及移植后过继免疫治疗有可能取长补短,提高疗效。 目的：观察自体骨髓混合H-2半相合异体骨髓移植后供体淋巴细胞输注+白细胞介素2治疗对小鼠白血病的疗效。 方法：将Balb/c小鼠经直线加速器照射3 Gy后分为白血病模型组、白血病模型照射组、混合移植组、自体骨髓移植组,均尾静脉注射5×10⁵ K562(GFP+/NeoR+)或K562(GFP-/NeoR-)细胞。7 d后6 Gy照射,自体骨髓移植组移植自体骨髓细胞或联合白细胞介素2治疗;混合移植组移植小鼠自体骨髓细胞混合1/10的H-2半相合异体骨髓细胞后应用白细胞介素2或联合供体淋巴细胞输注治疗。4周后行小鼠外周血及骨髓细胞形态检查,外周血细胞亚群、GFP及NeoR基因测定,肝、脾匀浆细胞GFP和NeoR基因测定。 结果与结论：白血病模型组小鼠因骨髓造血功能衰竭于20 d内全部死亡,白血病模型照射组小鼠因造血功能衰竭于14 d内全部死亡;自体骨髓移植组、混合移植组均有多少不等小鼠无白血病存活超过28 d,且混合骨髓移植后及自体骨髓移植后应用白细胞介素2治疗可提高白血病小鼠长期无病生存率,在此基础上联合供体淋巴细胞输注可更进一步提高白血病小鼠长期无病生存率。     

小鼠腹腔细胞的来源及其造血功能的研究

通过对受致死剂量照射的雌性小鼠,移植同种雄性小鼠的骨髓细胞,并用本实验室建立的制备小鼠腹腔细胞染色体的方法,分析雌性受体小鼠腹腔和骨髓细胞的Y染色体,证明小鼠腹腔细胞来源于骨髓中的造血细胞。用对骨髓中CFU-C和CFU-S的测定方法,证明小鼠腹腔细胞中含有一定数量的造血干细胞。它们在体外半固体培养中,可分化为单核巨噬细胞;在脾集落中,可分化为红系统和粒系统的细胞。当给受致死剂量照射的小鼠,移植较大量的腹腔细胞时,能延长其存活期。     

髓腔内骨髓移植诱导异基因小鼠皮肤移植耐受的研究

探讨髓腔内骨髓移植(IBM-BMT)对异基因小鼠皮肤移植耐受的诱导效果。受鼠为雌性C57BL/6(H-2b,B6)小鼠,于第0天接受60Coγ射线全身照射(TBI),4 h内输注雄性BALB/c(H-2d)小鼠来源的骨髓细胞(BMC),2 d后腹腔注射环磷酰胺(CTX)。通过皮肤移植、混合淋巴细胞反应(MLR)检测耐受状态,并通过骨髓染色体分析了解BMC的植入程度。结果显示,接受IBM-BMT的B6小鼠对BALB/c小鼠的皮肤移植物平均存活时间(MST)超过300 d,显著长于其余两组(P<0.001);MLR结果证明,实验组B6小鼠获得供体特异性耐受,在耐受小鼠骨髓中可检测到一定比例的Y染色体存在。以上表明髓腔内骨髓移植可以保证异基因骨髓细胞的植入并形成混合嵌合状态,从而有效地诱导免疫耐受。     

同基因造血干细胞移植免疫重建诱导小鼠皮肤移植耐受

背景：器官移植耐受的最佳效果是能够诱导对移植抗原的特异性免疫耐受。 目的：探讨小鼠异基因皮肤移植后,通过受体同基因造血干细胞移植重建免疫系统诱导移植皮肤免疫耐受的可行性。 方法：取BALB/c小鼠骨髓。以C57BL/6小鼠为供体,BALB/c小鼠为受体,进行异基因皮肤移植;32只受体鼠随机均分为4组：移植对照组、环孢素A组、照射组和骨髓移植组。 结果与结论：照射组小鼠10 d内全部死亡,外周血白细胞数呈持续性降低;而骨髓移植组小鼠长期存活,白细胞数全身照射后6 d降到最低,之后持续性增高,照射后21 d与环孢素A组比较差异无显著性意义(P > 0.05),移植皮肤存活时间显著长于其他各组(P < 0.01),其淋巴细胞浸润及组织结构破坏明显减少,小鼠脾细胞对供体小鼠脾细胞增殖反应显著降低。说明同基因骨髓细胞移植重建免疫系统可显著延长小鼠移植皮肤存活时间,可诱导供者特异性免疫耐受。     

骨髓源干细胞参与的血管内皮更新

背景：研究表明骨髓源干细胞可塑性强,但其参与组织更新及修复的机制在转分化及细胞融合间尚存在争议。 目的：通过性别交叉骨髓移植建立雌雄嵌合体小鼠模型,观察骨髓源性干细胞是否参与内皮细胞的更新并探讨其可能的机制。 方法：采用雌性C57BL/6-GFP小鼠为供体,雄性C57BL/6小鼠为受体进行骨髓移植建立嵌合体小鼠,并应用流式细胞术分析骨髓嵌合情况。骨髓移植后20周采用Y染色体荧光原位杂交法对脑、肾、肝、脾及心脏组织Y染色体进行标记,荧光显微镜观察各组织器官中血管内皮细胞Y染色体及绿荧光蛋白表达情况。 结果与结论：①嵌合体小鼠骨髓细胞流式细胞学检测显示移植骨髓后1周骨髓GFP⁺细胞为(7.48±1.38)%、4周时达(73.92±5.57)%,结果表明成功建立性别交叉骨髓移植模型。②骨髓移植后20周嵌合体小鼠脑、肾、肝和脾组织血管壁可见绿荧光蛋白表达,且部分细胞同时表达Y染色体,表明发生骨髓源细胞和血管内皮细胞融合。脑实质及心肌组织未见绿荧光蛋白表达。结果提示骨髓源干细胞可能通过细胞融合机制参与不同组织器官中血管内皮细胞的更新。     

骨髓源干细胞向损伤脑组织迁移的可能性

目的探讨骨髓源干细胞迁移至损伤脑组织的可能性。方法致死剂量照射的C57BL/6雌性小鼠，接受月龄相配的雄性小鼠骨髓移植。骨髓移植2个月后制作脑外伤模型，1、2、4和6周分批处死存活的动物。分别在外周血涂片和新鲜脑切片上用荧光原位杂交法检测Y染色体阳性细胞。结果在移植后6周的脑外伤病灶周围发现Y染色体阳性细胞。结论骨髓源干细胞可以迁移至脑外伤病灶周围，但这些细胞的性质需要进一步研究证实。     

多药耐药基因修饰的小鼠骨髓细胞对造血功能的保护作用

目的:将体外转染了人多药耐药基因(MDR1)的小鼠骨髓细胞,移植给经致死剂量照射的受体小鼠,观察该基因对小鼠造血功能的保护作用。方法:分离经5-Fu预处理的供体小鼠骨髓有核细胞,体外转染由逆转录病毒介导的人多药耐药基因MDR1,然后移植给经85Gy致死剂量照射的同系受体小鼠,以紫杉醇(Taxol)、长春新碱(VCR)、柔红霉素(DNR)筛选,观察小鼠血象、生存期和生存率变化,应用聚合酶链反应(PCR)和流式细胞仪(FCM)分析人多药耐药基因在小鼠中的整合与表达。结果:致死剂量辐照后,移植组小鼠造血功能逐渐恢复,未移植组15d内全部死亡。腹腔注射紫杉醇或静脉注射长春新碱、柔红霉素后,实验组生存率和生存期明显高于对照组(P<005)。表明MDR1基因能保护骨髓细胞,并且具有体内选择和富集作用,PCR分析提示,实验组外周血、骨髓、肝、脾组织中均检测到原病毒整合,RT-PCR与FCM检测到MDR1基因表达。结论:人MDR1基因修饰的小鼠骨髓细胞,能有效重建经致死剂量照射的受体小鼠造血功能,一定程度上保护骨髓免受化疗药物所致的细胞毒性作用。     

小鼠胎肝Sca-1+细胞分化为骨骼肌细胞

探讨小鼠胚胎肝组织中干细胞抗原-1阳性的细胞(Sca-1+细胞)向骨骼肌细胞分化的潜能.取14.5d的小鼠胎肝,制作细胞悬液;用单克隆免疫磁珠细胞分离技术分离Sca-1+细胞;用PCR鉴别Y染色体性别决定区域(SRY)基因序列;将2×103个雄性小鼠Sca-1+细胞输注给经致死剂量(10Gy)60钴全身照射的雌性小鼠体内;于移植后2个月,处死受体小鼠,取骨骼肌组织固定、制片;用免疫组织化学染色和荧光原位杂交检测雌性受体小鼠骨骼肌组织内供体小鼠胎肝Sca-1+细胞向骨骼肌细胞分化情况.结果在骨骼肌组织内发现存在Y染色体阳性的供体来源的细胞,同时呈现骨骼肌组织的部分特征,表型为Dystrophin+/Flt-1-/CD45-F4/80-.提示小鼠胎肝Sca-1+细胞(其中绝大部分是造血干细胞)具有向骨骼肌组织细胞分化的潜能.     

红景天多糖对骨髓抑制贫血小鼠外周血及骨髓细胞周期的影响

目的观察红景天多糖对骨髓抑制贫血小鼠外周血及骨髓细胞周期的影响，并探讨其造血调控作用机制。方法用全自动血细胞分析仪、白细胞计数法、流式细胞术（FCM）分别检测红景天多糖对骨髓抑制贫血小鼠外周血、骨髓有核细胞、骨髓细胞周期的影响。结果中剂量和高剂量红景天多糖能明显升高外周血白细胞（WBC）、红细胞（RBC）、血红蛋白（Hb）及骨髓有核细胞（BMCs）数，但对血小板的作用不明显。高剂量组可促进骨髓G0／G1期细胞向S期细胞以及S期细胞向G2／M期细胞的转化，增殖指数（PI）也明显升高。结论红景天多糖可能通过促使骨髓抑制贫血小鼠骨髓细胞通过G1期的限制点，进入细胞增殖周期，加速骨髓G0／G1期细胞向S期细胞、S期细胞向G2／M期细胞的转化，促进骨髓造血细胞增殖，提高外周血象，促进骨髓造血功能的恢复。     

Fluorescence in situ hybridization to determine engraftment status after murine bone marrow transplant.

The mouse Y-specific DNA sequence pY2 was used as a probe for fluorescence in situ hybridization (FISH) to evaluate murine hematopoietic tissues after sex-mismatched bone marrow transplant (BMT). The pY2 probe was localized to the long arm of the Y chromosome on BM metaphases. Hybridization of pY2 in FISH of interphase cells from BM, spleen, and thymus after BMT was compared with Southern blot analysis; both methods gave comparable results. Only FISH was able to analyze post-BMT peripheral blood (PB) samples successfully, and provides a useful method for following engraftment status in the mouse on an ongoing basis.     

当归补血汤对骨髓移植小鼠免疫功能重建的影响

目的 研究当归补血汤(DBT)对骨髓移植小鼠免疫功能重建作用的影响.方法 BALB/c小鼠一次性接受全身137Csγ线致死量照射8.5Gy,照射后0-4h内经尾静脉输注同基因骨髓细胞107/只,同时给于不同剂量DBT,每日灌胃1次,连续15d.于骨髓移植后30、60d,检测以下指标:外周血红细胞(RBC)、白细胞(WBC)计数,骨髓有核细胞计数,胸腺、脾细胞总数和相应淋巴细胞亚类,以及反映免疫细胞功能的迟发型超敏反应(DTH)、空斑形成细胞数(PFC)等.结果 经一定剂量DBT治疗的骨髓移植小鼠,其外周血中RBC、WBC计数,骨髓有核细胞计数,脾细胞和胸腺细胞总数,胸腺内各类细胞[双阴性细胞(DN)、双阳性细胞(DP)、单阳性细胞(SP)]的百分比值,与单纯骨髓移植小鼠比较差异有统计学意义(P<0.05),并且淋巴细胞的功能也得到进一步增强.到移植后60d,其各项指标进一步恢复.结论 当归补血汤可以促进骨髓移植小鼠免疫功能的恢复.     

放射损伤对于移植的骨髓间充质干细胞在受体大鼠不同器官中植入的影响

目的： 探讨放射损伤对于骨髓间充质干细胞（MSCs）移植后在受体大鼠不同器官中植入的影响以及可能的机制。方法：采用DNA缺口末端标记法(TUNEL)检测正常对照组和单纯放射组大鼠心脏、肾脏、肝脏、肺脏的细胞凋亡率。应用密度梯度离心法结合贴壁法提取雄性大鼠骨髓MSCs，培养后把MSCs移植到［60COγ］照射和未经照射的雌性大鼠体内，通过PCR和Y染色体荧光原位杂交（Y- FISH）示踪雄性大鼠MSCs在雌性大鼠体内的分布情况。结果：照射后大鼠心脏、肾脏、肝脏、肺脏细胞凋亡率显著高于对照组。PCR结果显示照射后移植MSCs的大鼠心脏、肾脏、肝脏、肺脏和外周血中可以扩增出Sry基因的DNA序列，而且Y- FISH显示照射后移植MSCs的大鼠在心脏、肾脏、肝脏、肺脏中可发现Y染色体阳性的细胞。但是未经照射行MSCs移植的大鼠在上述器官中未发现Y染色体阳性的细胞。结论：全身放射促进组织细胞的凋亡，并导致移植的MSCs在受体大鼠心脏、肾脏、肝脏和肺脏的植入。     

四种细胞移植重建C57BL雌鼠免疫功能的对比

背景：据报道肌肉来源的细胞能重建造血功能,还需要进一步观察其他系细胞是否也能重建造血功能。 目的：对比不同细胞对C57BL雌鼠造血功能恢复的作用。 方法：摘眼球取绿色荧光蛋白转基因雄鼠外周血,溶血后制成白细胞,再取脾脏、肝脏制成脾细胞和肝细胞悬液,同时制备骨髓细胞。将C57BL雌鼠半致死量射线照射后,回输4种细胞,并在移植后18,39,53 d检测外周血绿色荧光蛋白阳性细胞。同时标记CD4-PE和CD8-PE,并在移植后100 d杀鼠取骨髓检测Y染色体阳性率。 结果与结论：移植后18,39,53 d均在C57BL雌鼠外周血检测到绿色荧光蛋白阳性细胞;C57BL雌鼠外周血绿色荧光蛋白阳性细胞百分比：回输脾细胞和骨髓细胞>回输肝细胞>回输外周血白细胞。同时在回输脾细胞和骨髓细胞的C57BL雌鼠外周血中检测到绿色荧光蛋白和CD4双阳性细胞、绿色荧光蛋白和CD8双阳性细胞,而回输肝细胞和外周血白细胞的C57BL雌鼠外周血中几乎未检测到双阳性细胞。移植后100 d检测到的Y染色体阳性率与外周血中绿色荧光蛋白阳性率呈正相关。结果说明绿色荧光蛋白转基因雄鼠的外周血白细胞、脾细胞、肝细胞和骨髓细胞均有重建造血功能的作用,其中脾细胞与骨髓细胞作用相似,作用大于肝细胞,肝细胞作用大于白细胞。     

Optimal timing to repopulation of resident alveolar macrophages with donor cells following total body irradiation and bone marrow transplantation in mice

To determine the time required to repopulate mouse lungs with donor alveolar macrophages following total body irradiation (TBI) and bone marrow transplantation (BMT), C57Bl/6 mice were subjected to TBI with 900 cGy, followed by transplantation of bone marrow cells from mice expressing green fluorescent protein (GFP) in their somatic cells. The mice were euthanized at either 30 (n=5), 60 (n=5) or 90 (n=5) days following BMT. Thirty days following transplantation, 87.8 +/- 3.9% (mean +/- S.E.M.) circulating leukocytes in recipient mice were derived from the donor, as determined by fluorescence activated cell sorting (FACS) analysis for GFP. However, only 46.9 +/- 7.4% of the resident alveolar cells expressed GFP, indicating incomplete repopulation. By day 60 post-transplantation, the percentage of bronchoalveolar lavage fluid (BALF) cells expressing GFP reached 74.5 +/- 2.4%, remaining stable 90 days after transplantation (80.4 +/- 1.9%). We conclude that 60 days after TBI with 900 cGy and bone marrow transplantation, the majority of the lung resident alveolar macrophages is of donor origin. This study provides useful information regarding the time of reconstitution with donor alveolar macrophages in the pulmonary airspaces of recipient mice following marrow transplantation.     

Enhancement of allogeneic hematopoietic stem cell engraftment and prevention of GVHD by intra-bone marrow bone marrow transplantation plus donor lymphocyte infusion

We examined the effect of intra-bone marrow (IBM)-bone marrow transplantation (BMT) in conjunction with donor lymphocyte infusion (DLI) on the engraftment of allogeneic bone marrow cells (BMCs) in mice. Recipients that had received 6 Gy of radiation completely rejected donor BMCs, even when IBM-BMT was carried out. However, when BMCs were IBM injected and donor peripheral blood mononuclear cells (PBMNCs) were simultaneously injected intravenously (DLI), donor cell engraftment was observed 7 days after BMT and complete donor chimerism continued thereafter. It is of interest that the cells of recipient origin did not recover, and that the hematolymphoid cells, including progenitor cells (Lin-/c-kit+ cells) in the recipients, were fully reconstituted with cells of donor origin. The cells in the PBMNCs responsible for the donor BMC engraftment were CD8+. Recipients that had received 6 Gy of radiation, IBM-BMT, and DLI showed only a slight loss of body weight, due to radiation side effects, and had no macroscopic or microscopic symptoms of graft-versus-host disease. These findings suggest that IBM-BMT in conjunction with DLI will be a valuable strategy for allogeneic BMT in humans.     

Comparison of molecular and cytogenetic methods in the evaluation of engraftment following allogeneic bone marrow transplantation.

Cytogenetic evaluation of patients after bone marrow transplantation (BMT) has provided a standard method of documentation of hematopoietic engraftment. More recently, recombinant DNA technology has also been applied to determine engraftment status. In order to establish the relative utility of these methods in clinical practice we have directly compared the data from cytogenetic and recombinant DNA methods, evaluating engraftment status in 68 BMT recipients. Patients were evaluated pre-transplant, 30, 60, 90, and 180 days after BMT, and yearly thereafter for 1) the presence or absence of the Y chromosome in sex-mismatched allogeneic transplant recipients, 2) the presence or absence of the Philadelphia chromosome [t(9;22)] in patients transplanted for chronic myelogenous leukemia (CML), 3) restriction fragment length polymorphism (RFLP) profiles, and/or 4) clonal rearrangement of the bcr gene. Cytogenetic examination of unstimulated bone marrow and recombinant DNA tests of nucleated peripheral blood or bone marrow cells produce qualitatively similar data in the identification of patient and donor cells and/or normal and tumor cells. Differences in the results obtained by the two analytic methods were most often due to the restricted cell populations evaluable by cytogenetic studies of PHA-stimulated peripheral blood specimens. DNA analyses could frequently be applied at earlier intervals after transplantation and, in cases of graft rejection, when cell counts were low. Although recombinant DNA methods required fewer cells and demonstrated greater sensitivity in detection of minor cell populations in the majority of instances, the cytogenetic evaluation may complement the DNA studies and allow detection of additional chromosomal anomalies.     

The role of the donor in the repair of the marrow vascular niche following hematopoietic stem cell transplant

Bone marrow sinusoids maintain homeostasis between developing hematopoietic cells and the circulation, and they provide niches for hematopoietic progenitors. Sinusoids are damaged by chemotherapy and radiation. Hematopoietic stem cells (HSCs) have been shown to produce endothelial progenitor cells that contribute to the repair of damaged blood vessels. Because HSCs home to the marrow during bone marrow transplant, these cells may play a role in repair of marrow sinusoids. Here, we explore the role of donor HSCs in the repair of damaged sinusoids following hematopoietic stem cell transplant. We used three methods to test this role: (a) expression of platelet endothelial cell adhesion molecule to identify endothelial progenitors and the presence of the Y chromosome to identify male donor cells in female recipients; (b) presence of the Y chromosome to identify male donor cells in female recipients, and expression of the panendothelial marker mouse endothelial cell antigen-32 to identify sinusoidal endothelium; and (c) use of Tie-2/green fluorescent protein mice as donors or recipients and presence of Dil-Ac-LDL to identify sinusoids. We found that sinusoids were predominantly host-derived posttransplant. Donor cells spread along the marrow vasculature early post-transplant in a pattern that matched stromal-derived factor-1 expression. Furthermore, these engrafting progenitors were positioned to provide physical support, as well as growth and survival signals in the form of vascular-endothelial growth factor-A. Occasionally, donor cells provide cellular "patches" in the damaged sinusoids, although this occurred at a low level compared with hematopoietic engraftment. Donor support for the repair of the marrow vascular niche may be a critical first step of hematopoietic engraftment.     

真性红细胞增多症患者骨髓单个核细胞植入再生障碍性贫血小鼠

背景：真性红细胞增多症患者骨髓的高增殖低凋亡特性使其造血干细胞植入NOD/SCID小鼠后成功分化出粒红系细胞,但其能否植入并改善再生障碍性贫血小鼠造血功能,目前国内外尚未有报道。 目的：探讨JAK2阳性真性红细胞增多症患者骨髓单个核细胞植入后对再生障碍性贫血小鼠造血重建的影响。 方法：应用注射用重组人γ-干扰素联合白消安的方法建立再生障碍性贫血小鼠模型,随机分为实验组(n=10)和对照组(n=10),给药结束后第5天实验组经尾静脉输注真性红细胞增多症患者骨髓单个核细胞悬液,对照组同法输注等容积生理盐水。输注后第14天检测小鼠外周血常规、骨髓细胞形态、骨髓组织病理变化以及小鼠外周血和骨髓内CD45+细胞的百分含量。 结果与结论：输注后第14天,实验组小鼠血细胞计数三系减少,骨髓涂片可见散在淋巴细胞和早期造血细胞,骨髓组织活检可见骨髓增生减低,少量粒系细胞及幼红细胞,未见巨核细胞,与对照组比较,造血功能无明显改善。对照组小鼠外周血及骨髓均未检测到CD45+细胞,实验组小鼠外周血及骨髓均可检测到人源化的CD45+细胞,且骨髓中CD45+细胞比外周血高,提示JAK2V617F阳性真性红细胞增多症患者骨髓单个核细胞能成功植入再生障碍性贫血小鼠体内,但血常规、骨髓涂片及活检结果显示未能明显改善骨髓造血功能。  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Persistence of recipient lymphocytes in NOD mice after irradiation and bone marrow transplantation

The non-obese diabetic (NOD) mouse is a unique and invaluable model of autoimmune disease, in particular type 1 diabetes. Bone marrow transplantation as a therapy for type 1 diabetes has been explored in NOD mice. NOD mice require higher doses of conditioning irradiation for successful allogeneic bone marrow transplantation, suggesting that NOD hematopoietic cells are radioresistant compared to those of other mouse strains. However, studies of hematopoietic reconstitution in NOD mice are hampered by the lack of mice bearing a suitable cell-surface marker that would allow transferred cells or their progeny to be distinguished. In order to monitor hematopoietic reconstitution in NOD mice we generated congenic NOD mice that carry the alternative allelic form of the pan-leukocyte alloantigen CD45. Following irradiation and congenic bone marrow transplantation, we found that the myeloid lineage was rapidly reconstituted by cells of donor origin but substantial numbers of recipient T lymphocytes persisted even after supra-lethal irradiation. This indicates that radiation resistance in the NOD hematopoietic compartment is a property primarily of mature T lymphocytes.