Noizat-Pirenne F, Greenfeld J I, Hardy M A, Oluwole S F, De Groote D, Franchimont P
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
J Surg Res. 1996 Feb 15;61(1):267-74. doi: 10.1006/jsre.1996.0115.
Bone marrow mononuclear cell (BMMC) transplant may serve to produce donor specific tolerance for a coincident solid organ graft, but with the risk of graft versus host disease (GVHD). We examined in vitro the immunomodulatory effect of UVB on human BMMCs as potential prophylaxis against GVHD for clinical transplantation. After 10-200 J/m2 UVB-irradiation, BMMCs were examined by proliferative response (in mixed lymphocyte reaction and following phytohemagglutinin stimulation) and by cytokine profile. We also evaluated CFU-GM, CFU-GEMM, and BFU-E progenitor viability by 2-week methyl cellulose cultures following UVB-irradiation. Parallel studies were applied to marrow that was T-cell depleted by soybean agglutination (SBA) or by SBA and sheep erythrocyte rosetting (SBA-E-). We found that (1) UVB produces a dose-dependent inhibition of the proliferative response to stimulators by human BMMCs; (2) increasing doses of UVB-irradiation and increasing levels of T-cell depletion (TCD) are both inversely related to production of lymphokines (IL2, IL3, LIF, IFN-gamma, and GMCSF) and (3) T-cell depletion, but not UVB-irradiation, decreases the production of monokines (IL1, TNF, IL6). Progenitor cell viability was decreased but preserved at 100 J/m2 of UVB. Our findings suggest that UVB compares favorably with TCD as a technique for inhibition of GVHD and therefore that UVB-modulation of bone marrow (BM) inoculum may be useful in the prevention of GVHD in clinical bone marrow transplantation accompanying a solid organ graft.
骨髓单个核细胞（BMMC）移植可能有助于对同时进行的实体器官移植物产生供体特异性耐受，但存在移植物抗宿主病（GVHD）的风险。我们在体外研究了紫外线B（UVB）对人BMMC的免疫调节作用，作为临床移植中预防GVHD的潜在方法。在10 - 200 J/m² UVB照射后，通过增殖反应（在混合淋巴细胞反应和植物血凝素刺激后）和细胞因子谱来检测BMMC。我们还通过UVB照射后2周的甲基纤维素培养来评估CFU - GM、CFU - GEMM和BFU - E祖细胞的活力。对通过大豆凝集素（SBA）或SBA和绵羊红细胞玫瑰花结形成（SBA - E - ）去除T细胞的骨髓进行了平行研究。我们发现：（1）UVB对人BMMC对刺激物的增殖反应产生剂量依赖性抑制；（2）UVB照射剂量增加和T细胞耗竭（TCD）水平增加均与淋巴细胞因子（IL2、IL3、LIF、IFN - γ和GMCSF）的产生呈负相关；（3）T细胞耗竭而非UVB照射会降低单核细胞因子（IL1、TNF、IL6）的产生。祖细胞活力降低，但在100 J/m² UVB时仍得以保留。我们的研究结果表明，作为一种抑制GVHD的技术，UVB与TCD相比具有优势，因此骨髓（BM）接种物的UVB调节可能有助于预防临床骨髓移植伴随实体器官移植物时的GVHD。
