title: 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.
abstract: 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 [1,300 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 CD(4)(+) and CD(8)(+) T cell, 1.72 and 1.27-fold respectively at week 3 compared with TCD-BMT group (P < 0.01); make CD(4)(+)/CD(8)(+) 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).
  
  
  CONCLUSIONS
  The gene transduced stromal cell line QXMSC1-IL-2 + IL-3 is able to accelerate T-cell immunity in allo-BMT mice.
authors.affiliation: Department of Immunology, Peking University Health Science Center, Beijing 100083, China.
authors.forename: Ai-ling
authors.initials: AL
authors.lastname: Li
authors.forename: Ji-yang
authors.initials: JY
authors.lastname: Jiang
authors.forename: Jian-bo
authors.initials: JB
authors.lastname: Ma
authors.forename: Guang-ming
authors.initials: GM
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Hao
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Shu-Sheng
authors.initials: SS
authors.lastname: Xie
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002460:Cell Line; D022801:Complementarity Determining Regions; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D007376:Interleukin-2 / Q000235:genetics*; D007377:Interleukin-3 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014184:Transplantation, Homologous
chemical_list: D022801:Complementarity Determining Regions; D007376:Interleukin-2; D007377:Interleukin-3; D004318:Doxycycline