[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.].
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Costimulation with Dex and IL-2 can selectively expand the functional CD4(+)CD25(+)FOXP3(+) Treg in vivo, which can suppress acute GVHD.
Hematology Department, Affiliated Huashan Hospital of Fudan University, Shanghai 200040, China.
Yan-Hui
YH
Xie
Run-Hua
RH
Song
Wei-Lian
WL
Geng
Min
M
Wu
D000818:Animals; D003907:Dexamethasone; D051858:Forkhead Transcription Factors; D006086:Graft vs Host Disease; D006801:Humans; D007376:Interleukin-2; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory
D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D003907:Dexamethasone