OBJECTIVETo investigate the effect of murine mesenchymal stem cells (mMSC) on immunoproliferative response of spleen cells.

METHODSMitogen (Con A, 20 microg/ml) or irradiated (20 Gy) allogeneic spleen cells (from BALB/c or C57BL/6 mouse depending on the responder cells) were used as stimulators. Proliferations of the responder cells were determined with MTT on day 3 after culture at 37 degrees C, 5% CO2 humidified atmosphere. The ratios of CD4+/CD8+ and CD4+CD25+ cells were analyzed with FACS assay, and the levels of cytokines in supernatants with ELISA.

RESULTS1) mMSC inhibited the response of both syngeneic and allogeneic splenic cells to ConA. At the ratio of mMSC to splenic cells being 1: 1, the inhibition rate reached 84.21%. With the ratio decreasing, the inhibition rate decreased. 2) mMSC inhibited the response of both syngeneic and allogeneic splenic cells to alloantigen. When the ratio of mMSC to responder cells was 1: 10, the inhibition rate was as high as 88.07%. 3) mMSC could increase the ratio of CD4+/ CD8+ T cells and the percentage of CD4+ CD25+ cells in splenic cells. These abilities were in a dose-dependent manner and non-MHC antigen restricted. 4) mMSC decreased interleukin (IL) -2, interferon (IFN)-gamma, while increased TGF-beta1 and IL-4 in the co-culture system.

CONCLUSIONmMSC can suppress proliferative response of splenic cells to mitogen and alloantigen, increase the ratio of CD4+/CD8+ and the proportion of CD4+ CD25+ in T cells, decrease the secretion of proinflammatory cytokines and increase the anti inflammatory cytokines in a dose-dependent and non-MHC antigen restricted manner.