Gowing H, Lawler M, Hagenbeek A, McCann S R, Pamphilon D H, Hudson J, van Weelden H, Braakman E, Martens A C
Institute of Hematology, Erasmus University Rotterdam, The Netherlands.
Blood. 1996 Feb 15;87(4):1635-43.
Ultraviolet B (UVB) light is known to be immunosuppressive, but, probably because of a small UVC component in the emission spectra of some of the UVB lamps used, reports vary on effective dose levels. To prevent potentially lethal graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation, alloreactive donor T-cell activity must be suppressed. In this study, a narrow wavelength UVB lamp (TL01, 312 nm peak emission) was used to determine what doses of UVB were required to abolish rat lymphocyte proliferation while simultaneously preserving rat bone marrow progenitor cell and primitive hematopoietic stem cell viability. Lymphocyte proliferation, as measured by 3H-Thymidine incorporation, in response to lectin stimulation was abolished below detection at doses greater than 3,500 J/m2. When T-cell clonogenicity was measured in a limiting dilution assay, a small fraction (0.6%) was maintained at doses up to 4,000 J/m2. Cytotoxic T-lymphocyte (CTL) activity was reduced after treatment with 4,000 J/m2, but a significant level of cytotoxicity was still maintained. Natural killer cell cytolytic activity was not affected by doses up to 4,000 J/m2. At 4,000 J+m2 there was a 10% survival of colony-forming units-granulocyte-macrophage; a 1% and 4% survival of day-8 and day-12 colony-forming units-spleen, respectively; and 11% survival of marrow repopulating ability cells. Up to 25% of late cobblestone area forming cells (4 to 5 weeks), reflecting the more immature hematopoietic stem cells, were preserved in bone marrow treated with 4,000 J/m2, indicating that early stem cells are less sensitive to UVB damage than are more committed progenitor cells. Thus, a potential therapeutic window was established at approximately 4,000 J/m2 using this light source, whereby the potentially GVHD-inducing T cells were suppressed, but a sufficient proportion of the cells responsible for engraftment was maintained.
已知中波紫外线（UVB）具有免疫抑制作用，但可能由于所使用的一些UVB灯发射光谱中存在少量的短波紫外线（UVC）成分，关于有效剂量水平的报道各不相同。为预防异基因骨髓移植后潜在致命的移植物抗宿主病（GVHD），必须抑制同种异体反应性供体T细胞活性。在本研究中，使用窄波长UVB灯（TL01，峰值发射波长312nm）来确定需要何种剂量的UVB才能消除大鼠淋巴细胞增殖，同时保持大鼠骨髓祖细胞和原始造血干细胞的活力。通过3H-胸腺嘧啶核苷掺入法测定，当剂量大于3500J/m2时，对凝集素刺激的淋巴细胞增殖在检测限以下被消除。当在有限稀释试验中测量T细胞克隆形成能力时，在剂量高达4000J/m2时仍维持一小部分（0.6%）。用4000J/m2处理后，细胞毒性T淋巴细胞（CTL）活性降低，但仍维持显著水平的细胞毒性。自然杀伤细胞的溶细胞活性在剂量高达4000J/m2时不受影响。在4000J/m2时，粒细胞-巨噬细胞集落形成单位的存活率为10%；第8天和第12天脾集落形成单位的存活率分别为1%和4%；骨髓重建能力细胞的存活率为11%。在用4000J/m2处理的骨髓中，高达25%的晚期鹅卵石区域形成细胞（4至5周）得以保留，这反映了更不成熟的造血干细胞，表明早期干细胞对UVB损伤的敏感性低于更定向的祖细胞。因此，使用该光源在约4000J/m2时建立了一个潜在的治疗窗口，由此抑制了潜在诱导GVHD的T细胞，但维持了足够比例的负责植入的细胞。
