Combination of paeoniae radix and cnidii rhizoma prolonged survival of fully mismatched cardiac allografts and generated regulatory cells in mice.
In previous studies, we have demonstrated that Tokishakuyakusan (TJ-23) can prolong the survival of allogeneic cardiac grafts and induce regulatory T cells. In this study we investigated the effects of Paeoniae radix and Cnidii rhizoma, two components of TJ-23, on alloimmune responses in a murine cardiac transplantation model and whether the two agents have synergistic effect. CBA mice underwent transplantation of a C57BL/6 heart and received oral administration of 2 g/kg/day of Paeoniae radix, Cnidii rhizoma, or the mixture of two agents from the day of transplantation until 7 days afterward. Naïve CBA mice rejected C57BL/6 cardiac graft acutely (median survival time (MST): 7 days). Paeoniae radix and Cnidii rhizoma prolonged C57BL/6 allograft survival (MSTs: 13.5 and 15.5 days, resp.). However, the mixture of two agents prolonged C57BL/6 allograft survival indefinitely (MST > 100 days). Secondary CBA recipients given whole splenocytes from primary combination-treated CBA recipients with B6 cardiac allografts 30 days after grafting had prolonged survival of B6 hearts (MST: 33 days). Flow cytometry studies showed that the CD4(+)CD25(+)Foxp3(+) regulatory cell population was increased in combination-treated recipients. Combination of Paeoniae radix and Cnidii rhizoma induced hyporesponsiveness to fully allogeneic cardiac allografts and may generate CD4(+)CD25(+)Foxp3(+) regulatory cells in our model.
Department of Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan ; Department of Cardiovascular and Thoracic Surgery, the 4th Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang, Harbin, Heilongjiang 150001, China.
Xiangyuan
0000-0003-2252-8343
X
Jin
Department of Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan ; Department of General Surgery, the 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, Harbin, Heilongjiang 150086, China.
Lei
L
Yu
Department of Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan ; Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Masateru
M
Uchiyama
Department of Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan ; Department of Cardiovascular Surgery, the 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, Harbin, Heilongjiang 150086, China.
Enzhi
0000-0002-4265-0058
E
Yin
Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Tadanori
T
Harada
Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Ken
K
Otsuka
Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Shigefumi
S
Matsuyama
Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Tomohiro
T
Imazuru
Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Tomoki
T
Shimokawa
Department of Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Masanori
M
Niimi