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Human dendritic cells produce TGF-beta 1 under the influence of lung carcinoma cells and prime the differentiation of CD4+CD25+Foxp3+ regulatory T cells.
J Immunol. 2009 Mar 01; 182(5):2795-807.JI

Abstract

Dendritic cells (DCs) have a central role in the development of adaptive immune responses, including antitumor immunity. Factors present in the tumor milieu can alter the maturation of DCs and inhibit their capacity to activate T cells. Using gene expression analysis, we found that human DCs increased the expression of TGF-beta1 transcripts following culture with human lung carcinoma cells (LCCs). These DCs produced increased amounts of TGF-beta1 protein compared with DCs not exposed to tumor cells. LCCs also decreased the expression of CD86 and HLA-DR by immature DCs. Furthermore, LCCs decreased CD86 expression and the production of TNF-alpha and IL-12 p70 by mature DCs. Moreover, LCCs also converted mature DCs into cells producing TGF-beta1. These TGF-beta1-producing DCs were poor at eliciting the activation of naive CD4(+) T cells and sustaining their proliferation and differentiation into Th1 (IFN-gamma(+)) effectors. Instead, TGF-beta1-producing DCs demonstrated an increased ability to generate CD4(+)CD25(+)Foxp3(+) regulatory T cells that suppress the proliferation of T lymphocytes. These results identify a novel mechanism by which the function of human DCs is altered by tumor cells and contributes to the evasion of the immune response.

Authors+Show Affiliations

Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. i.dumitriu@sgul.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19234174

Citation

Dumitriu, Ingrid E., et al. "Human Dendritic Cells Produce TGF-beta 1 Under the Influence of Lung Carcinoma Cells and Prime the Differentiation of CD4+CD25+Foxp3+ Regulatory T Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 182, no. 5, 2009, pp. 2795-807.
Dumitriu IE, Dunbar DR, Howie SE, et al. Human dendritic cells produce TGF-beta 1 under the influence of lung carcinoma cells and prime the differentiation of CD4+CD25+Foxp3+ regulatory T cells. J Immunol. 2009;182(5):2795-807.
Dumitriu, I. E., Dunbar, D. R., Howie, S. E., Sethi, T., & Gregory, C. D. (2009). Human dendritic cells produce TGF-beta 1 under the influence of lung carcinoma cells and prime the differentiation of CD4+CD25+Foxp3+ regulatory T cells. Journal of Immunology (Baltimore, Md. : 1950), 182(5), 2795-807. https://doi.org/10.4049/jimmunol.0712671
Dumitriu IE, et al. Human Dendritic Cells Produce TGF-beta 1 Under the Influence of Lung Carcinoma Cells and Prime the Differentiation of CD4+CD25+Foxp3+ Regulatory T Cells. J Immunol. 2009 Mar 1;182(5):2795-807. PubMed PMID: 19234174.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human dendritic cells produce TGF-beta 1 under the influence of lung carcinoma cells and prime the differentiation of CD4+CD25+Foxp3+ regulatory T cells. AU - Dumitriu,Ingrid E, AU - Dunbar,Donald R, AU - Howie,Sarah E, AU - Sethi,Tariq, AU - Gregory,Christopher D, PY - 2009/2/24/entrez PY - 2009/2/24/pubmed PY - 2009/4/22/medline SP - 2795 EP - 807 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 182 IS - 5 N2 - Dendritic cells (DCs) have a central role in the development of adaptive immune responses, including antitumor immunity. Factors present in the tumor milieu can alter the maturation of DCs and inhibit their capacity to activate T cells. Using gene expression analysis, we found that human DCs increased the expression of TGF-beta1 transcripts following culture with human lung carcinoma cells (LCCs). These DCs produced increased amounts of TGF-beta1 protein compared with DCs not exposed to tumor cells. LCCs also decreased the expression of CD86 and HLA-DR by immature DCs. Furthermore, LCCs decreased CD86 expression and the production of TNF-alpha and IL-12 p70 by mature DCs. Moreover, LCCs also converted mature DCs into cells producing TGF-beta1. These TGF-beta1-producing DCs were poor at eliciting the activation of naive CD4(+) T cells and sustaining their proliferation and differentiation into Th1 (IFN-gamma(+)) effectors. Instead, TGF-beta1-producing DCs demonstrated an increased ability to generate CD4(+)CD25(+)Foxp3(+) regulatory T cells that suppress the proliferation of T lymphocytes. These results identify a novel mechanism by which the function of human DCs is altered by tumor cells and contributes to the evasion of the immune response. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/19234174/Human_dendritic_cells_produce_TGF_beta_1_under_the_influence_of_lung_carcinoma_cells_and_prime_the_differentiation_of_CD4+CD25+Foxp3+_regulatory_T_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=19234174 DB - PRIME DP - Unbound Medicine ER -