Xing Haizhou, Liu Shiqin, Chen Xue, Fang Fang, Wu Xueqiang, Zhu Ping
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Hematology, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, China.
Immunobiology. 2017 Apr;222(4):658-663. doi: 10.1016/j.imbio.2016.12.003. Epub 2016 Dec 26.
To examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion.
Mouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1×10 of the labeled cells were intravenously injected into a recipient. At 6h, 24h, 72h and 120h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected. CFSE+, CFSE-, CD3+, CD8+, CD4+, CD19+, NK1.1+, CD25+, and CD127+ lymphocytes in those samples were analyzed by flow cytometry. The distribution of donor T cells, B cells, NK cells, helper T cells, cytotoxic T cells, and recipient regulatory T cells in the tissues were then analyzed.
Maternal lymphocytes were more likely to survive in offspring. At 120h after infusion, the percentages of maternal cells in the offspring were 0.52±0.11% in lymph nodes, 0.97±0.04% in peripheral blood, and 0.97±0.11% in the spleen. Few donor cells, if any, were detected in these tissues at 120h after aunt to child, father to child, and unrelated allogeneic infusions were performed. The subtype proportion of donor lymphocytes changed significantly in the recipient tissues. Recipient Treg cells increased in the mother to child group, but not in the aunt to child, father to child, and unrelated allogeneic groups, suggesting a decreased cellular immune response to allogeneic cells in the mother to child group. At 120h after the infusion, no donor cells were detected in the recipient livers and thymuses of all groups, implying that donor cells were barely able to colonize in the liver and thymus.
Specific immune tolerance to maternal lymphocytes exists in offspring. An infusion of maternal donor lymphocytes may produce a relatively persistent effect of adoptive immunotherapy with reduced side-effects.
研究供体淋巴细胞输注后母源淋巴细胞与子代组织之间的免疫耐受情况。
将雌性BALB/c小鼠与雄性C57小鼠交配建立小鼠模型。用羧基荧光素琥珀酰亚胺酯（CFSE）标记来自不同遗传背景供体的脾淋巴细胞，并将1×10个标记细胞静脉注射到受体体内。在输注后6小时、24小时、72小时和120小时，收集受体脾脏、肝脏、胸腺、淋巴结和外周血中的单核细胞。通过流式细胞术分析这些样本中CFSE+、CFSE-、CD3+、CD8+、CD4+、CD19+、NK1.1+、CD25+和CD127+淋巴细胞。然后分析组织中供体T细胞、B细胞、NK细胞、辅助性T细胞、细胞毒性T细胞和受体调节性T细胞的分布。
母源淋巴细胞更易在子代中存活。输注后120小时，子代淋巴结中母源细胞的百分比为0.52±0.11%，外周血中为0.97±0.04%，脾脏中为0.97±0.11%。在进行姑侄、父子和无关异体输注后120小时，在这些组织中几乎未检测到供体细胞（若有）。供体淋巴细胞的亚型比例在受体组织中发生显著变化。母胎组中受体调节性T细胞增加，而姑侄组、父子组和无关异体组中未增加，这表明母胎组中对异体细胞的细胞免疫反应降低。输注后120小时，所有组的受体肝脏和胸腺中均未检测到供体细胞，这意味着供体细胞几乎无法在肝脏和胸腺中定植。
子代对母源淋巴细胞存在特异性免疫耐受。输注母源供体淋巴细胞可能产生相对持久的过继免疫治疗效果，且副作用减少。
