Prevention of transfusion-associated graft-versus-host disease by photochemical treatment.
Prevention of transfusion-associated graft-versus-host disease by photochemical treatment.
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DOI：
10.1182/blood.v93.9.3140.409a42_3140_3147
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发表时间：
1999-05
期刊：
影响因子：
20.3
通讯作者：
J. Grass;Tamim Wafa;A. Reames;D. Wages;L. Corash;J. Ferrara;Lily Lin
中科院分区：
文献类型：
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作者：
J. Grass;Tamim Wafa;A. Reames;D. Wages;L. Corash;J. Ferrara;Lily Lin
用补骨脂素S-59和长波紫外线进行光化学处理，可灭活人浓缩血小板中高滴度的污染病毒、细菌和白细胞。本研究采用典型的亲本F1小鼠输血模型，在体内评价了PCT预防输血相关移植物抗宿主病(TA-GVHD)的有效性。四个处理组的受体小鼠输注10(8)个脾白细胞。(1)对照组接受同基因脾白细胞输注；(2)GVHD组小鼠接受未经处理的同种异体脾白细胞；(3)伽玛射线照射组小鼠接受伽马照射(2,500cGy)异基因脾白细胞；(4)PCT组小鼠接受150micromol/L S-59和2.1J/cm2 UVA处理的异基因脾白细胞。在输血后10周的观察期内，使用多种生物学和临床指标监测受者小鼠移植后移植物抗宿主病(TA-GVHD)的发展：外周血细胞水平、脾大小、供者T细胞植入、胸腺细胞密度、TA-GVHD的临床体征(体重减轻、活动、姿势、毛发质地、皮肤完整性)以及肝、脾、骨髓和皮肤的组织学损害。对照组的小鼠保持健康，没有可检测到的疾病。GVHD组小鼠出现了TA-GVHD的临床和组织学损害，包括全血细胞减少、明显的脾肿大、消瘦、移植供体来源的T细胞和胸腺发育不良。相比之下，接受2,500cGy伽玛射线或150微摩尔/L S-59和2.1J/cm2 UVA治疗的脾白细胞输注的小鼠仍然健康，没有发生可检测到的TA-GVHD。在体外T细胞增殖试验中，PCT灭活了10(5.1)个以上的小鼠T细胞。因此，除了灭活PC中高水平的致病病毒和细菌外，这些数据表明PCT是预防TA-GVHD的有效替代伽玛射线照射。
Photochemical treatment (PCT) with the psoralen S-59 and long wavelength ultraviolet light (UVA) inactivates high titers of contaminating viruses, bacteria, and leukocytes in human platelet concentrates. The present study evaluated the efficacy of PCT to prevent transfusion-associated graft-versus-host disease (TA-GVHD) in vivo using a well-characterized parent to F1 murine transfusion model. Recipient mice in four treatment groups were transfused with 10(8) splenic leukocytes. (1) Control group mice received syngeneic splenic leukocyte transfusions; (2) GVHD group mice received untreated allogeneic splenic leukocytes; (3) gamma radiation group mice received gamma irradiated (2,500 cGy) allogeneic splenic leukocytes; and (4) PCT group mice received allogeneic splenic leukocytes treated with 150 micromol/L S-59 and 2.1 J/cm2 UVA. Multiple biological and clinical parameters were used to monitor the development of TA-GVHD in recipient mice over a 10-week posttransfusion observation period: peripheral blood cell levels, spleen size, engraftment by donor T cells, thymic cellularity, clinical signs of TA-GVHD (weight loss, activity, posture, fur texture, skin integrity), and histologic lesions of liver, spleen, bone marrow, and skin. Mice in the control group remained healthy and free of detectable disease. Mice in the GVHD group developed clinical and histological lesions of TA-GVHD, including pancytopenia, marked splenomegaly, wasting, engraftment with donor derived T cells, and thymic hypoplasia. In contrast, mice transfused with splenic leukocytes treated with (2,500 cGy) gamma radiation or 150 micromol/L S-59 and 2.1 J/cm2 UVA remained healthy and did not develop detectable TA-GVHD. Using an in vitro T-cell proliferation assay, greater than 10(5.1) murine T cells were inactivated by PCT. Therefore, in addition to inactivating high levels of pathogenic viruses and bacteria in PC, these data indicate that PCT is an effective alternative to gamma irradiation for prevention of TA-GVHD.