The roles of antigen-specificity, responsiveness to transforming growth factor-beta and antigen-presenting cell subsets in tumour-induced expansion of regulatory T cells.
Summary of "The roles of antigen-specificity, responsiveness to transforming growth factor-beta and antigen-presenting cell subsets in tumour-induced expansion of regulatory T cells."
Summary In this study we investigated the impact of several factors on the expansion of natural regulatory T (nTreg) cells by tumours, including antigen specificity, transforming growth factor-beta (TGF-beta) signalling and the antigen-presenting cell subsets responsible for expansion. We found that antigen non-specific expansion of nTreg cells is tumour cell line-dependent. Although both antigen-specific and non-specific pathways can contribute to expansion, the migration of activated nTreg cells to tumour tissues is strictly antigen-dependent. Intact TGF-beta signalling on nTreg cells is also essential for tumour-induced expansion. Finally, for stimulation of resting antigen-specific CD4 T cells, CD11c(+) cells purified from tumour-draining lymph nodes were more potent than CD11b(+) cells, suggesting that dendritic cells are the key antigen-presenting cell subset involved in cross-presentation of tumour antigens. This study not only provides an in vivo system in which cross-talk between nTreg cells and tumours can be explored but also reveals novel aspects of tumour immune evasion.
Affiliation
Cancer Immunotherapy Group, Section of Immunobiology, Department of Medicine, Imperial College London, London, UK.
Journal Details
This article was published in the following journal.
Name: Immunology
ISSN: 1365-2567
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20722761
- DOI: http://dx.doi.org/10.1111/j.1365-2567.2010.03328.x
Medical and Biotech [MESH] Definitions
Receptors, Transforming Growth Factor Beta
Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.
Transforming Growth Factors
Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA.
Transforming Growth Factor Beta1
A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.
Transforming Growth Factor Beta2
A TGF-beta subtype that was originally identified as a GLIOBLASTOMA-derived factor which inhibits the antigen-dependent growth of both helper and CYTOTOXIC T LYMPHOCYTES. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta2 and TGF-beta2 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor.
Tgf-beta Superfamily Proteins
A large family of cell regulatory proteins which are structurally related to TRANSFORMING GROWTH FACTOR BETA. The superfamily is subdivided into at least three related protein families: BONE MORPHOGENETIC PROTEINS; GROWTH DIFFERENTIATION FACTORS; and TRANSFORMING GROWTH FACTORS.
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