Combination of dexamethasone with IL-2 selectively induces the expansion of CD4(+)CD25(+)FOXP3(+) regulatory T cells in vivo and suppresses graft versus host disease / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To establish a method for increasing T regulatory cells (Treg) in the graft by using in vivo treatment with dexamethasone (Dex) plus IL-2 and observe its suppressing effect on graft-versus-host-disease (GVHD) in mice.</p><p><b>METHODS</b>After treatment of male C57BL/6N mice (donor) with Dex (5 mgxkg(-1)xd(-1)) combined with IL-2 (300 000 IUxmouse(-1)xday(-1)) for three days, spleen mononuclear cells were isolated for flow cytometry analysis of CD4(+)CD25(+) POXP3(+) Treg cells. The allogeneic lymphocytes were transplanted from male C57BL/6N mice to female BALB/c mice aged 8-12 weeks. GVHD and survival time were investigated after transplantation. Donor-derived hematopoiesis reconstituted in recipient mice was detected by Y-chromosome-specific PCR and H-2K(b) by flow cytometry.</p><p><b>RESULTS</b>Administration of Dex and IL-2 markedly expanded functional CD4(+)CD25(+)FOXP3(+) Treg cells in murine spleen, the number of which in treated group was (24.2 +/- 7.6)% while in control group was (4.0 +/- 0.8)% (P = 0.01). The ratio of Treg to effector T cells (Teff) increased obviously in the treated group (0.43 +/- 0.15 vs 0.14 +/- 0.01, P = 0.01). In a murine allogeneic lymphocyte transplantation model, the grafts from donor with combined treatment of Dex and IL-2 led to a longer survival time than that from the control group (median survival time > 60 d vs 12 d, P = 0.0045), while the mortality rate was decreased (29.4% vs 71.4%, P < 0.05).</p><p><b>CONCLUSION</b>Costimulation with Dex and IL-2 can selectively expand the functional CD4(+)CD25(+)FOXP3(+) Treg in vivo, which can suppress acute GVHD.</p>