论文部分内容阅读
Background After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient The purpose of this study was to observe the effects of the gene-engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 on the reconstitution of T-cell immunity in allo-BMT mice Methods The bone marrow stromal cell line QXMSC1 was co-transfected with IL-2 and IL-3 genes using a Tet-on gene expression system T lymphocyte subset counts per spleen were analyzed by flow cytometry Lymphocyte proliferation response to ConA was examined to evaluate T-cell function CDR3 spectratyping techniques were performed to evaluate TCR repertoire diversity at various time points post-transplantation Results Gene engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 could express IL-2 and IL-3 (1300 ng·day -1 ·10 -6 cells and 1100 ng·day -1 ·10 -6 cells, respectively) under the control of doxycycline QXMSC1-IL-2+IL-3 in combination with allogeneic bone marrow could significantly increase the counts of CD4 + and CD8 + T cell, 1.72 and 1.27-fold respectively at week 3 compared with TCD-BMT group ( P <0.01); make CD4 +/CD8 + ratio return to normal level at week 4; enhance splenocytes mitotic response to ConA ( P <0.01), and accelerate restoration of TCR repertoire diversity in the lethally irradiated mice ( P <0.05) KH*2/5DConclusion The gene transduced stromal cell line QXMSC1-IL-2+IL-3 is able to accelerate T-cell immunity in allo-BMT mice
Background After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient The purpose of this study was to observe the effects of the gene-engineered bone marrow stromal cell line QXMSC1-IL-2 + IL-3 on the reconstitution of T-cell immunity in allo-BMT mice Methods The bone marrow stromal cell line QXMSC1 was co-transfected with IL-2 and IL-3 genes using a Tet-on gene expression system T lymphocyte subset counts per spleen were analyzed by flow cytometry Lymphocyte proliferation response to ConA was examined to evaluate T-cell function CDR3 spectratyping techniques were performed to evaluate TCR repertoire diversity at various time points post-transplantation Results Gene engineered bone marrow stromal cell line QXMSC1-IL-2 IL-3 could express IL-2 and IL-3 (1300 ng · day -1 · 10 -6 cells and 1100 ng · day -1 · 10 -6 cells, respectively) under the control of doxycycline QXMSC1-IL-2 + IL-3 in combination with allogeneic bone marrow could significantly increase the counts of CD4 + and CD8 + T cells, 1.72 and 1.27-fold respectively at week 3 compared with TCD-BMT group (P <0.01); make CD4 + / CD8 + return to normal level at week 4; enhance splenocytes mitotic response to ConA (P <0.01), and accelerate restoration of TCR repertoire diversity in the lethally irradiated mice (P <0.05) KH * 2 / 5DConclusion The gene transduced stromal cell line QXMSC1-IL-2 + IL-3 is able to accelerate T-cell immunity in allo-BMT mice