[Influence of donor T(reg) cells on GVHD and hematopoietic reconstitution after allogeneic bone marrow transplantation in mice]

Abstract

In order to explore the influence of purified donor regulatory T cells (T(Reg) cells) infused after allogeneic bone marrow transplantation (allo-BMT) on GVHD and hematopoietic reconstitution of mice, an allo-BMT model of C(57)BL/6-->BALB/c mice was established. CD4(+)CD25(+)T(Reg) cells were purified through bead-magnetic activated cells separated from donor mice peripheral blood. The recipient mice were randomly divided into three groups: CD4(+)CD25(+) T cells, CD4(+)CD25(-) T cells and RPMI 1640 culture medium. These cells and RPMI 1640 were infused into recipient mice by caudal veins at about 6 to 8 hours after allo-BMT respectively. Incidence of GVHD, pathological lesion of liver, spleen, small intestine, survival time and hematopoietic reconstitution in the recipients were observed after allo-BMT. The results showed that the time for WBC > 1.0 x 10(9)/L was (8.14 +/- 3.26) days, (17.62 +/- 5.71) days, (19.81 +/- 6.77) days and the time for Plt > 20.0 x 10(9)/L was (5.29 +/- 1.34) days, (8.97 +/- 3.44) days, (9.52 +/- 3.92) days in T(Reg) positive cell group, T(Reg) negative cell group and the blank control group respectively, and the recovery times of WBC and Plt in T(Reg) positive cell group were faster than that in T(Reg) negative cell group and the blank control group (P < 0.05). The scores of GVHD were (1.33 +/- 0.58), (1.80 +/- 0.27), (1.93 +/- 0.45) in three groups of mice at about 15 days after allo-BMT, respectively, the GVHD in T(Reg) positive cell group was slighter than that in T(Reg) negative cell group and the blank control group (P < 0.05). It was found that GVHD pathologic manifestations of the liver, spleen and small intestine in T(Reg) positive cell group were slighter in a certain extent than those in other two groups at about (25 - 30) days after allo-BMT. The mean survival time in three groups was (41.45 +/- 17.88) days, (18.75 +/- 14.39) days and (25.67 +/- 16.84) days after allo-BMT, respectively, which in the T(Reg) positive cell group was significantly longer than that in other two groups (P < 0.05). It is concluded that donor-T(Reg) cell infusion can mitigate the GVHD so as to reach hematopoietic reconstitution and prolong survival time after allo-BMT in mice.