Bone marrow stromal cell line co-transfected with IL-2 and IL-3 genes can accelerate restoration of T-cell immunity in allo-BMT mice

摘要

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). Conclusion The gene transduced stromal cell line QXMSC1-IL-2 + IL-3 is able to accelerate T-cell immunity in allo-BMT mice.