Sirolimus promotes differentiation and proliferation of regulatory T cells in mouse heart transplantation model

Xie Jiangping; Zhang Xiliang; Liu Gang; Wu Shihe; Wang Yuhong

doi:10.3969/j.issn.1674-7445.2015.01.006

Volume 6 Issue 1

Jan. 2015

Turn off MathJax

Article Contents

Article Navigation > ORGAN TRANSPLANTATION > 2015 > 6(1): 26-30

Xie Jiangping, Zhang Xiliang, Liu Gang, et al. Sirolimus promotes differentiation and proliferation of regulatory T cells in mouse heart transplantation model[J]. ORGAN TRANSPLANTATION, 2015, 6(1): 26-30. doi: 10.3969/j.issn.1674-7445.2015.01.006

Citation:

PDF( 245 KB)

Sirolimus promotes differentiation and proliferation of regulatory T cells in mouse heart transplantation model

doi: 10.3969/j.issn.1674-7445.2015.01.006

Department of General Surgery, Navy General Hospital, Beijing 100048, China

More Information

Corresponding author: Wu Shihe, Email:luckyy666@126.com
Received Date: 2014-11-22
Available Online: 2021-01-19
Publish Date: 2015-01-15

Abstract

Abstract

Objective To investigate the impacts of sirolimus (SRL) on the survival time of graft and the differentiation and proliferation of regulatory T cell (Treg) of spleen in mouse heterotopic heart transplantation model. Methods Male BALB/c→C57BL/6 mice cervical heterotopic heart transplantation model was established by Cuff method. The mice were divided into 3 groups randomly with 10 mice in each group. The control group received no treatment of special medicine after operation. Mice in SRL group were gavaged with SRL 10 mg/(kg·d) at 1-14 d after operation. Mice in ciclosporin (CsA) group were gavaged with CsA 30 mg/(kg·d)at 1-14 d after operation. The survival time of cardiac grafts were recorded. The spleen was procured after asystole of cardiac graft or 14 d after operation. Mononuclear cells were isolated and the proportion of CD4⁺CD25⁺Treg in CD4⁺ T cell(CD4⁺ CD25⁺ Treg%) were detected by flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of Foxp3 messenger ribonucleic acid (mRNA) semi-quantitatively. Results Compared with the control group, the survival time of cardiac grafts prolonged significantly in SRL and CsA group (all in P < 0.01), but no significant difference was observed between SRL and CsA group(P> 0.05). Compared with the control group, CD4⁺CD25⁺ Treg% significantly decreased in the spleen of CsA group and significantly increased in SRL group (all in P < 0.01). And significant difference was observed between SRL and CsA group (P < 0.01). Expression of Foxp3 mRNA of T lymphocyte in the spleen of SRL group was significantly higher than those in control and CsA group (P < 0.01). And expression of Foxp3 mRNA in control group was significantly higher than that in CsA group (P < 0.01). Conclusions In mouse heart transplantation model, SRL can prolong the survival time of graft and promote the proliferation and growth of CD4⁺ CD25⁺ Treg to facilitate the establishment of immune tolerance.
- Regulatory T cell,
- Mouse,
- Heart transplantation,
- Sirolimus,
- Ciclosporine

FullText(HTML)

References(22)

References

[1]	Gassel HJ, Kauczock J, Martens N, et al. Tolerance induction following orthotopic rat liver transplantation:cytokine production by CD4⁺ T cells determines the immunological response[J]. Transplant Proc, 2002, 34(5):1429-1430. doi: 10.1016/S0041-1345(02)02915-9
[2]	Waldmann H, Graca L, Cobbold S, et al. Regulatory T cells and organ transplantation[J]. Semin Immunol, 2004, 16(2):119-126. doi: 10.1016/j.smim.2003.12.007
[3]	Wood KJ, Sawitzki B. Interferon gamma:a crucial role in the function of induced regulatory T cells in vivo[J]. Trends Immunol, 2006, 27(4):183-187. doi: 10.1016/j.it.2006.02.008
[4]	张英才, 杨卿, 汪国营, 等.人脐带间充质干细胞和他克莫司联合应用对T淋巴细胞增殖的影响[J/CD].中华肝脏外科手术学电子杂志, 2013, 2(6):390-393. Zhang YC, Yang Q, Wang GY, et al. Impact of human umbilical cord mesenchymal stem cells combined with tacrolimus on T lymphocytes proliferation[J/CD]. Chin J Hepatic Surg:Electr Edit, 2013, 2(6):390-393.
[5]	Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4⁺ CD25⁺ FoxP3⁺ regulatory T cells[J]. Blood, 2005, 105(12):4743-4748. doi: 10.1182/blood-2004-10-3932
[6]	Strauss L, Whiteside TL, Knights A, et al. Selective survival of naturally occurring human CD4⁺CD25⁺Foxp3⁺ regulatory T cells cultured with rapamycin[J].J Immunol, 2007, 178(1):320-329. doi: 10.4049/jimmunol.178.1.320
[7]	马东霞, 王璐, 赵越, 等.OX 40信号调节抑制小鼠CD4⁺CD25⁺调节性T淋巴细胞Foxp3的表达[J].中华器官移植杂志, 2013, 34(7):424-427. http://d.wanfangdata.com.cn/Periodical/zhqgyz98201307011 Ma DX, Wang L, Zhao Y, et al. OX 40 stimulation down-regulates the expression of Foxp3 in CD4⁺CD25⁺ regulatory T cells[J]. Chin J Organ Transplant, 2013, 34(7):424-427. http://d.wanfangdata.com.cn/Periodical/zhqgyz98201307011
[8]	Cardenas ME, Zhu D, Heitman J. Molecular mechanisms of immunosuppression by cyclosporine, FK506, and rapamycin[J]. Curr Opin Nephrol Hypertens, 1995, 4(6):472-477. doi: 10.1097/00041552-199511000-00002
[9]	Powell JD, Pollizzi KN, Heikamp EB, et al. Regulation of immune responses by mTOR[J]. Annu Rev Immunol, 2012, 30:39-68. doi: 10.1146/annurev-immunol-020711-075024
[10]	Araki K, Youngblood B, Ahmed R. The role of mTOR in memory CD8⁺ T-cell differentiation[J]. Immunol Rev, 2010, 235(1):234-243. doi: 10.1111/(ISSN)1600-065X
[11]	Waickman AT, Powell JD. mTOR, metabolism, and the regulation of T-cell differentiation and function[J]. Immunol Rev, 2012, 249(1):43-58. doi: 10.1111/imr.2012.249.issue-1
[12]	Walsh PT, Buckler JL, Zhang J, et al. PTEN inhibits IL-2 receptor-mediated expansion of CD4⁺CD25⁺ Tregs[J]. J Clin Invest, 2006, 116(9):2521-2531. http://europepmc.org/articles/PMC1550279
[13]	Haxhinasto S, Mathis D, Benoist C. The AKT mTOR axis regulates de novo differentiation of CD4⁺Foxp3⁺ cells[J]. J Exp Med, 2008, 205(3):565-574. doi: 10.1084/jem.20071477
[14]	Fox CJ, Hammerman PS, Thompson CB. The Pim kinases control rapamycin-resistant T cell survival and activation[J]. J Exp Med, 2005, 201(2):259-266. doi: 10.1084/jem.20042020
[15]	Basu S, Golovina T, Mikheeva T, et al. Cutting edge:Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin[J].J Immunol, 2008, 180(9):5794-5798. doi: 10.4049/jimmunol.180.9.5794
[16]	Kim JM, Rudensky A. The role of the transcription factor Foxp3 in the development of regulatory T cells[J]. Immunol Rev, 2006, 212:86-98. doi: 10.1111/imr.2006.212.issue-1
[17]	Khattri R, Cox T, Yasayko SA, et al. An essential role for Scurfin in CD4⁺ CD25⁺ T regulatory cells[J]. Nat Immunol, 2003, 4(4):337-342. doi: 10.1038/ni909
[18]	Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3[J]. Science, 2003, 299(5609):1057-1061. doi: 10.1126/science.1079490
[19]	Choi BM, Pae HO, Jeong YR, et al. Critical role of heme oxygenase-1 in Foxp3-mediated immune suppression[J].Biochem Biophys Res Commun, 2005, 327(4):1066-1071. doi: 10.1016/j.bbrc.2004.12.106
[20]	Sekiya T, Kashiwagi I, Yoshida R, et al. Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis[J].Nat Immunol, 2013, 14(3):230-237. doi: 10.1038/ni.2520
[21]	Chen Z, Barbi J, Bu S, et al. The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3[J].Immunity, 2013, 39(2):272-285. doi: 10.1016/j.immuni.2013.08.006
[22]	Zhang P, Tey SK, Koyama M, et al. Induced regulatory T cells promote tolerance when stabilized by rapamycin and IL-2 in vivo[J]. J Immunol, 2013, 191(10):5291-303. doi: 10.4049/jimmunol.1301181

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(3)

Get Citation

PDF

XML

Article Metrics

Article views (121) PDF downloads(6)

Sirolimus promotes differentiation and proliferation of regulatory T cells in mouse heart transplantation model

doi: 10.3969/j.issn.1674-7445.2015.01.006

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Sirolimus promotes differentiation and proliferation of regulatory T cells in mouse heart transplantation model

doi: 10.3969/j.issn.1674-7445.2015.01.006

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Export File

Citation

Format

Content