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Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3.
J Exp Med 2003; 198(12):1875-86JE

Abstract

CD4+CD25+ regulatory T cells (Treg) are instrumental in the maintenance of immunological tolerance. One critical question is whether Treg can only be generated in the thymus or can differentiate from peripheral CD4+CD25- naive T cells. In this paper, we present novel evidence that conversion of naive peripheral CD4+CD25- T cells into anergic/suppressor cells that are CD25+, CD45RB-/low and intracellular CTLA-4+ can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor beta (TGF-beta). Although transcription factor Foxp3 has been shown recently to be associated with the development of Treg, the physiological inducers for Foxp3 gene expression remain a mystery. TGF-beta induced Foxp3 gene expression in TCR-challenged CD4+CD25- naive T cells, which mediated their transition toward a regulatory T cell phenotype with potent immunosuppressive potential. These converted anergic/suppressor cells are not only unresponsive to TCR stimulation and produce neither T helper cell 1 nor T helper cell 2 cytokines but they also express TGF-beta and inhibit normal T cell proliferation in vitro. More importantly, in an ovalbumin peptide TCR transgenic adoptive transfer model, TGF-beta-converted transgenic CD4+CD25+ suppressor cells proliferated in response to immunization and inhibited antigen-specific naive CD4+ T cell expansion in vivo. Finally, in a murine asthma model, coadministration of these TGF-beta-induced suppressor T cells prevented house dust mite-induced allergic pathogenesis in lungs.

Authors+Show Affiliations

Cellular Immunology Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. wchen@dir.nidcr.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14676299

Citation

Chen, WanJun, et al. "Conversion of Peripheral CD4+CD25- Naive T Cells to CD4+CD25+ Regulatory T Cells By TGF-beta Induction of Transcription Factor Foxp3." The Journal of Experimental Medicine, vol. 198, no. 12, 2003, pp. 1875-86.
Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003;198(12):1875-86.
Chen, W., Jin, W., Hardegen, N., Lei, K. J., Li, L., Marinos, N., ... Wahl, S. M. (2003). Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. The Journal of Experimental Medicine, 198(12), pp. 1875-86.
Chen W, et al. Conversion of Peripheral CD4+CD25- Naive T Cells to CD4+CD25+ Regulatory T Cells By TGF-beta Induction of Transcription Factor Foxp3. J Exp Med. 2003 Dec 15;198(12):1875-86. PubMed PMID: 14676299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. AU - Chen,WanJun, AU - Jin,Wenwen, AU - Hardegen,Neil, AU - Lei,Ke-Jian, AU - Li,Li, AU - Marinos,Nancy, AU - McGrady,George, AU - Wahl,Sharon M, PY - 2003/12/17/pubmed PY - 2004/1/24/medline PY - 2003/12/17/entrez SP - 1875 EP - 86 JF - The Journal of experimental medicine JO - J. Exp. Med. VL - 198 IS - 12 N2 - CD4+CD25+ regulatory T cells (Treg) are instrumental in the maintenance of immunological tolerance. One critical question is whether Treg can only be generated in the thymus or can differentiate from peripheral CD4+CD25- naive T cells. In this paper, we present novel evidence that conversion of naive peripheral CD4+CD25- T cells into anergic/suppressor cells that are CD25+, CD45RB-/low and intracellular CTLA-4+ can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor beta (TGF-beta). Although transcription factor Foxp3 has been shown recently to be associated with the development of Treg, the physiological inducers for Foxp3 gene expression remain a mystery. TGF-beta induced Foxp3 gene expression in TCR-challenged CD4+CD25- naive T cells, which mediated their transition toward a regulatory T cell phenotype with potent immunosuppressive potential. These converted anergic/suppressor cells are not only unresponsive to TCR stimulation and produce neither T helper cell 1 nor T helper cell 2 cytokines but they also express TGF-beta and inhibit normal T cell proliferation in vitro. More importantly, in an ovalbumin peptide TCR transgenic adoptive transfer model, TGF-beta-converted transgenic CD4+CD25+ suppressor cells proliferated in response to immunization and inhibited antigen-specific naive CD4+ T cell expansion in vivo. Finally, in a murine asthma model, coadministration of these TGF-beta-induced suppressor T cells prevented house dust mite-induced allergic pathogenesis in lungs. SN - 0022-1007 UR - https://www.unboundmedicine.com/medline/citation/14676299/Conversion_of_peripheral_CD4+CD25__naive_T_cells_to_CD4+CD25+_regulatory_T_cells_by_TGF_beta_induction_of_transcription_factor_Foxp3_ L2 - http://jem.rupress.org/cgi/pmidlookup?view=long&pmid=14676299 DB - PRIME DP - Unbound Medicine ER -