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Research Article

Induction of Regulatory T Cells and Prolongation of Fully Allogeneic Cardiac Grafts by Herbal Medicine, Shohangekabukuryo-to

Enzhi Yin1,2, Masateru Uchiyama1,3, Xiangyuan Jin1,4 and Masanori Niimi1*

1Department of Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan

2Department of Cardiovascular Surgery, Hospital of Harbin Medical University, 246 Xuefu Road, Nangang, Harbin, Heilongjiang 150086, China

3Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan

4Department of Thoracic Surgery, the 3rd Affiliated Hospital of Harbin Medical University, 150 Haping Road, Nangang, Harbin, Heilongjiang 150081, China

*Corresponding Author:
Masanori Niimi
MD, PhD. Department of Surgery
Teikyo University, 2-11-1 Kaga
Itabashi-ku, Tokyo 173-8605
Japan
Tel: +81-3-3964-1228
Fax: +81-3-3962-2128
E-mail: [email protected]

Received date: August 24, 2015 Accepted date: September 26, 2015 Published date: October 3, 2015

Citation:Yin E, Uchiyama M, Jin X, Niimi M (2015) Induction of Regulatory T Cells and Prolongation of Fully Allogeneic Cardiac Grafts by Herbal Medicine, Shohangekabukuryo-to. Altern Integr Med 4:198. doi:10.4172/2327-5162.1000198

Copyright: ©2015 Yin E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: Shohangekabukuryo-to (Tsumura Japan [TJ]-21) is well known as an herbal medicine with few side effects to treat vomiting, nausea, acute and chronic gastritis, and hyperemesis of pregnancy in Japan. In this study, we performed fully allogeneic cardiac grafts in mice to investigate the effect of TJ-21 on alloimmune responses. Methods: CBA (H2k) mice underwent transplantation of a C57BL/6 (H2b) heart and received oral administration of 0.02, 0.2 and 2 g/kg per day of TJ-21 from the day of operation until 7 days afterward. Adoptive transfer study was performed to determine whether regulatory cells were generated. Histologic and cell proliferation studies, flow cytometry analyses and cytokine measurements were also performed. Results: Compared to untreated CBA mice rejected C57BL/6 hearts acutely (median survival time [MST], 8 days), MST of allografts from TJ-21-treated mice was prolonged (MST, 77 days). Moreover, adoptive transfer of whole splenocytes from TJ-21-treated allograft CBA recipients had prolongation of allograft survival in secondary recipients (MST, 53 days). Flow cytometry study showed TJ-21-treated mice had an increased CD4+CD25+Foxp3+ cell population. Cell proliferation showed that interleukin-2 (IL-2) and interferon-γ were inhibited in TJ-21-treated mice, whereas IL-4 and IL-10 were increased. Conclusions: In summary, TJ-21 could induce hyporesponsiveness of fully MHC-mismatched cardiac allografts and generate regulatory cells.

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