再生障碍性贫血小鼠模型中免疫活化T细胞动力学研究

OBJECTIVE: To explore the dynamic changes of donor derived T cells at different time points in the aplastic anemia mouse model. METHODS: 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. RESULTS: 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. CONCLUSION: 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.