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Medical Oncology

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01.09.2010 | Original Paper

Low molecular weight fraction secreted by SKOV3 cells expands peripheral CD4+CD25+ regulatory T cells and enhances their suppressive capacity

verfasst von: Xiao Li, Xiaoyun Wan, Yuyan Mao, Weiguo Lu, Xing Xie

Erschienen in: Medical Oncology | Ausgabe 3/2010

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Abstract

The increase of CD4+CD25+ regulatory T cells in patients with ovarian carcinoma has been verified. Here we investigated the effects of supernatant derived from ovarian carcinoma cell SKOV3 on peripheral regulatory T cells. Supernatant from SKOV3 was collected and fractionated into three different molecular weight fractions (MWFs). The proliferation of the CD4+CD25+ regulatory T cells cultured in complete RPMI 1640 medium with the different stimulators was detected. The phenotype (GITR and CTLA-4) of natural and expanded CD4+CD25+ T cells was detected by flow cytometry. Foxp3 mRNA expression of low MWF-expanded CD4+CD25+ T cells was detected by RT-PCR. Those expanded CD4+CD25+ regulatory T cells showed enhanced capacity to suppress CD4+CD25− T proliferation and increased expression of GITR and CTLA-4. In brief, low molecular weight fraction of supernatant secreted by SKOV3 could expand peripheral CD4+CD25+ regulatory T cells and enhance their suppressive function.

Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F, et al. Thymus and autoimmunity: production of CD25⁺CD4⁺ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol. 1999;162(9):5317–26.PubMed

Apostolou I, Sarukhan A, Klein L, von Boehmer H. Origin of regulatory T cells with known specificity for antigen. Nat Immunol. 2002;3(8):756–63.PubMed

Zhang X, Izikson L, Liu L, Weiner HL. Activation of CD25⁺ CD4⁺ regulatory T cells by oral antigen administration. J Immunol. 2001;167(8):4245–53.PubMed

Thornton AM, Shevach EM. CD4⁺CD25⁺ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med. 1998;188(2):287–96.CrossRefPubMed

Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G. Ex Vivo isolation and characterization of CD4⁺CD25⁺ T cells with regulatory properties from human blood. J Exp Med. 2001;193(11):1303–10.CrossRefPubMed

Thornton AM, Shevach EM. Suppressor effector function of CD4⁺CD25⁺ immunoregulatory T cells is antigen nonspecific. J Immunol. 2000;164(1):183–90.PubMed

Curiel TJ, Couko G, Zou L. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–9.CrossRefPubMed

Steitz J, Bruck J, Lenz J, Knop J, Tuting T. Depletion of CD25⁺CD4⁺ T cells and treatment with tyrosinase-related protein 2-transduced dendritic cells enhance the interferon α-induced CD8⁺ T cell dependent immune defense of B 16 melanoma. Cancer Res. 2001;61(24):8643–6.PubMed

Seo N, Hayakawa S, Takigawa M, Tokura Y. Interleukin-10 expressed at early tumor sites induces subsequent generation of CD4⁺ T-regulatory cells and systemic collapse of antitumour immunity. Immunology. 2001;103(4):449–57.CrossRefPubMed

10.

Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, et al. Regulatory CD4⁺CD25⁺ T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res. 2001;61(12):4766–72.PubMed

11.

Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res. 2003;9(2):606–12.PubMed

12.

Li Xiao, Ye Dafeng, Xie Xing, Chen Huaizeng, Lu Weiguo. Increase of CD4+CD25+ regulatory T cell in the patients with ovarian carcinoma. Cancer Invest. 2005;23(5):399–403.PubMed

13.

Walker MR, Kasprowicz DJ, Gersuk VH, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25− T cells. J Clin Invest. 2003;112(9):1437–43.PubMed

14.

Li Xiao, Ye Feng, Chen Huaizeng, Lu Weiguo, Wan Xiaoyun, Xie Xing. Human ovarian carcinoma cells generate CD4+CD25+ regulatory T cells from peripheral CD4+CD25− T cells through secreting TGF-β. Cancer Lett. 2007;253(1):144–53.CrossRefPubMed

15.

Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH. Identification and functional characterization of human CD4+CD25+ T cells with regulatory properties isolated from peripheral blood. J Exp Med. 2001;193(11):1285–94.CrossRefPubMed

16.

Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S. Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol. 2002;3(2):135–42.CrossRefPubMed

17.

Levings MK, Sangregorio R, Sartirana C, Moschin AL, Battaglia M, Orban PC, et al. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells. J Exp Med. 2002;196(10):1335–46.CrossRefPubMed

18.

Birebent B, Lorho R, Lechartier H, de Guibert S, Alizadeh M, Vu N, et al. Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA-4 expression. Eur J Immunol. 2004;34(12):3485–96.CrossRefPubMed

19.

Dujardin HC, Burlen-Defranoux O, Boucontet L, Vieira P, Cumano A, Bandeira A. Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells. Proc Natl Acad Sci USA. 2004;101(40):14473–8.CrossRefPubMed

20.

Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for scurfin in CD4+CD25+ T regulatory cells. Nat Immunol. 2003;4(4):337–42.CrossRefPubMed

21.

Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330–6.CrossRefPubMed

22.

Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057–61.CrossRefPubMed

23.

Li B, Saouaf SJ, Samanta A, Shen Y, Hancock WW, Greene MI. Biochemistry and therapeutic implications of mechanisms involved in FOXP3 activity in immune suppression. Curr Opin Immunol. 2007;19(5):583–8.CrossRefPubMed

Titel: Low molecular weight fraction secreted by SKOV3 cells expands peripheral CD4+CD25+ regulatory T cells and enhances their suppressive capacity
verfasst von: Xiao Li
Xiaoyun Wan
Yuyan Mao
Weiguo Lu
Xing Xie
Publikationsdatum: 01.09.2010
Verlag: Springer US
Erschienen in: Medical Oncology / Ausgabe 3/2010
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-009-9255-3

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Low molecular weight fraction secreted by SKOV3 cells expands peripheral CD4+CD25+ regulatory T cells and enhances their suppressive capacity

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