Histone deacetylase inhibitor affected CD4+CD25+Foxp3+ cells in a mouse model of acute graftversus host disease

Zhu Jie-lin; Zhang Peng

doi:10.3969/j.issn.2095-4344.2014.49.007

Abstract：BACKGROUND:Prevention and treatment of graftversus host disease and elevation of graft survival rate are core problems needed to be solved in alogenic hematopoietic stem cel transplantation. Thus, it is necessary to find a new immunosuppressant. Recent studies showed that histone deacetylase inhibitor has immunomodulatory effects. OBJECTIVE:To observe the effects of histone deacetylase inhibitor SAHA on acute graftversus host disease in mice and the immunomodulatory effects. METHODS: C57BL/6(H-2b)→BALB/C(H-2d) was selected as donor and recipient of complete alotransplantation. At 3, 5, 7, 9 and 11 days after transplantion, mice in the treatment group were intraperitonealy given SAHA (35 mg/kg) (0.2 mL). Mice in the control group were intraperitonealy given sterile water 0.2 mL/time. Flow cytometry, real-time quantitative PCR and pathology were used to compare the clinical manifestations, survival time and CD4+CD25+Foxp3+ cel percentage of acute graftversus host disease in mice of both groups. RESULTS AND CONCLUSION:In the treatment group, the time of acute graftversus host disease was delayed and the extent was reduced and survival time was longer compared with the control group. Survival rate was significantly higher in the treatment group than in the control group (P < 0.05). After transplantation, the proportions of CD4+CD25+Foxp3+ cels gradualy increased with prolonged time in the treatment group. On the contrary, the proportions of CD4+CD25+Foxp3+ cels gradualy decreased with prolonged time in the control group (P < 0.05). Above data suggested that SAHA delayed the occurrence of acute graftversus host disease and lessened the severity of acute graft versus host disease possibly through elevating the proportion of CD4+CD25+Foxp3+ cels.