Li W W, Li R N, Zhang L L, Ma Q Y, Li H Y, Wang W J, Mao J, Chu Y J, Yuan W P, Shi J
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2022 Jul 14;43(7):581-586. doi: 10.3760/cma.j.issn.0253-2727.2022.07.009.
To explore the dynamic changes of donor derived T cells at different time points in the aplastic anemia mouse model. The aplastic anemia mouse model was induced and then the proportion of infiltrated donor derived T cells in spleen and bone marrow, expression of activation molecular markers, cell cycle and functional subsets were measured by flow cytometry at different time points to evaluate the functional status of T cells in different periods. ①T cell immune-mediated aplastic anemia mouse model was successfully established by half lethal dose irradiation combined with major histocompatibility antigen (MHC) haploidentical lymph node cells infusion. ②The donor derived T cells began to infiltrate significantly in the spleen of aplastic anemia mouse from the 3rd day after transplantation and the ratio of CD4(+)/CD8(+) gradually inverted. After the 5th day, they gradually entered the bone marrow, predominated by CD8(+) cells. ③The expression peak of CD69 in donor CD4(+) cells was later than that in CD8(+) cells. The trend of CD25 expression in CD4(+) cells was the same as that in CD8(+) cells, but the expression level in CD8(+) cells was higher than CD4(+) cells. ④The proportion of donor CD4(+) cells in S/G(2)/M phase reached the peak in spleen, about 12%, within 3 days after transplantation, while a higher level in CD8(+) cells, which was about 20%. And the proportion of both CD4(+) and CD8(+) cells in S/G(2)/M phase increased again after entering bone marrow, which was continued to be higher in CD8(+) cells than that in CD4(+) cells after 3 days of transplantation. ⑤Immune activated T cells in the spleen rapidly differentiated into effector memory T cells (T(EM)) after a short central memory T cell (T(CM)) stage. After entering the bone marrow, some T(EM) differentiated into effector cells to further function. In the aplastic anemia mouse model, donor derived T cells activated rapidly after entering the allogenic recipient, reached its proliferation booming period and differentiated into T(EM) cells within 5 days. After 5 days, they began to enter the bone marrow to continue proliferate and damage hematopoiesis.
探讨再生障碍性贫血小鼠模型中不同时间点供体来源T细胞的动态变化。建立再生障碍性贫血小鼠模型，然后在不同时间点通过流式细胞术检测脾脏和骨髓中浸润的供体来源T细胞比例、活化分子标志物表达、细胞周期及功能亚群，以评估不同时期T细胞的功能状态。①通过半致死剂量照射联合主要组织相容性抗原（MHC）半相合淋巴结细胞输注成功建立T细胞免疫介导的再生障碍性贫血小鼠模型。②供体来源T细胞在移植后第3天开始在再生障碍性贫血小鼠脾脏中显著浸润，CD4(+)/CD8(+)比值逐渐倒置。第5天后，它们逐渐进入骨髓，以CD8(+)细胞为主。③供体CD4(+)细胞中CD69的表达峰值晚于CD8(+)细胞。CD4(+)细胞中CD25的表达趋势与CD8(+)细胞相同，但CD8(+)细胞中的表达水平高于CD4(+)细胞。④供体CD4(+)细胞在S/G(2)/M期的比例在移植后3天内在脾脏中达到峰值，约为12%，而CD8(+)细胞中的比例更高，约为20%。进入骨髓后，CD4(+)和CD8(+)细胞在S/G(2)/M期的比例再次增加，移植3天后CD8(+)细胞中的比例继续高于CD4(+)细胞。⑤脾脏中的免疫活化T细胞在经历短暂的中枢记忆T细胞（T(CM)）阶段后迅速分化为效应记忆T细胞（T(EM)）。进入骨髓后，一些T(EM)分化为效应细胞以进一步发挥作用。在再生障碍性贫血小鼠模型中，供体来源T细胞进入同种异体受体后迅速活化，在5天内达到增殖高峰期并分化为T(EM)细胞。5天后，它们开始进入骨髓继续增殖并损害造血功能。
