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In-vitro generation and characterisation of murine CD4+CD25+ regulatory T cells with indirect allospecificity.
Int Immunopharmacol 2006; 6(13-14):1883-8II

Abstract

Naturally arising CD4(+)CD25(+) regulatory T cells play a pivotal role in the prevention of autoimmunity and in the induction of donor-specific transplantation tolerance. Harnessing regulatory cells for potential adoptive cell therapy is hampered by their lack of antigen-specificity and their limited numbers. Here we describe the generation and expansion of murine CD4(+)CD25(+) T cells with antigen-specificity for an K(d) peptide as potential reagents for adoptive cell therapy in promoting donor-specific transplantation tolerance. Using bone marrow-derived autologous dendritic cells pulsed with the K(d) peptide, we generated T cell lines from purified CD4(+)CD25(+) T cells from C56BL/6 mice. The T cell lines expressed high level of CD25 and low level of CD45RB and CD69. They maintained the expression of CD62L, GITR, CTLA-4 and more importantly FoxP3. The CD4(+)CD25(+) T cell lines were anergic after TCR stimulation and produced little cytokine such as IL-2 and IFN-gamma. Importantly, they were more potent than freshly isolated CD4(+)CD25(+) T cells in suppressing proliferation and cytokine secretion by effector CD4(+) T cells. Furthermore, the CD4(+)CD25(+) T cell lines could be expanded to large cell numbers and maintained in culture up to 1 year. The K(d)-specific CD4(+)CD25(+) T cell lines will be invaluable in devising a strategy for the induction of cardiac transplantation tolerance in wild-type B6 mice carrying a full mismatch BALB/c heart.

Authors+Show Affiliations

Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17161341

Citation

Tsang, Julia, et al. "In-vitro Generation and Characterisation of Murine CD4+CD25+ Regulatory T Cells With Indirect Allospecificity." International Immunopharmacology, vol. 6, no. 13-14, 2006, pp. 1883-8.
Tsang J, Jiang S, Tanriver Y, et al. In-vitro generation and characterisation of murine CD4+CD25+ regulatory T cells with indirect allospecificity. Int Immunopharmacol. 2006;6(13-14):1883-8.
Tsang, J., Jiang, S., Tanriver, Y., Leung, E., Lombardi, G., & Lechler, R. I. (2006). In-vitro generation and characterisation of murine CD4+CD25+ regulatory T cells with indirect allospecificity. International Immunopharmacology, 6(13-14), pp. 1883-8.
Tsang J, et al. In-vitro Generation and Characterisation of Murine CD4+CD25+ Regulatory T Cells With Indirect Allospecificity. Int Immunopharmacol. 2006 Dec 20;6(13-14):1883-8. PubMed PMID: 17161341.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In-vitro generation and characterisation of murine CD4+CD25+ regulatory T cells with indirect allospecificity. AU - Tsang,Julia, AU - Jiang,Shuiping, AU - Tanriver,Yakup, AU - Leung,Eva, AU - Lombardi,Giovanna, AU - Lechler,Robert I, Y1 - 2006/09/01/ PY - 2006/07/18/received PY - 2006/07/22/accepted PY - 2006/12/13/pubmed PY - 2007/3/14/medline PY - 2006/12/13/entrez SP - 1883 EP - 8 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 6 IS - 13-14 N2 - Naturally arising CD4(+)CD25(+) regulatory T cells play a pivotal role in the prevention of autoimmunity and in the induction of donor-specific transplantation tolerance. Harnessing regulatory cells for potential adoptive cell therapy is hampered by their lack of antigen-specificity and their limited numbers. Here we describe the generation and expansion of murine CD4(+)CD25(+) T cells with antigen-specificity for an K(d) peptide as potential reagents for adoptive cell therapy in promoting donor-specific transplantation tolerance. Using bone marrow-derived autologous dendritic cells pulsed with the K(d) peptide, we generated T cell lines from purified CD4(+)CD25(+) T cells from C56BL/6 mice. The T cell lines expressed high level of CD25 and low level of CD45RB and CD69. They maintained the expression of CD62L, GITR, CTLA-4 and more importantly FoxP3. The CD4(+)CD25(+) T cell lines were anergic after TCR stimulation and produced little cytokine such as IL-2 and IFN-gamma. Importantly, they were more potent than freshly isolated CD4(+)CD25(+) T cells in suppressing proliferation and cytokine secretion by effector CD4(+) T cells. Furthermore, the CD4(+)CD25(+) T cell lines could be expanded to large cell numbers and maintained in culture up to 1 year. The K(d)-specific CD4(+)CD25(+) T cell lines will be invaluable in devising a strategy for the induction of cardiac transplantation tolerance in wild-type B6 mice carrying a full mismatch BALB/c heart. SN - 1567-5769 UR - https://www.unboundmedicine.com/medline/citation/17161341/In_vitro_generation_and_characterisation_of_murine_CD4+CD25+_regulatory_T_cells_with_indirect_allospecificity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(06)00222-0 DB - PRIME DP - Unbound Medicine ER -