CD25-expressing Th17 cells mediate CD8+ T cell suppression in CTLA-4 dependent mechanisms in pancreatic ductal adenocarcinoma.
Exp Cell Res
; 360(2): 384-389, 2017 11 15.
Article
em En
| MEDLINE
| ID: mdl-28942020
ABSTRACT
The tumor-associated immune response is governed by the signalling events of various regulatory molecules, one of which is the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). In conventional T cells, CTLA-4 could outcompete CD28 in binding to CD80/86 but does not produce a co-stimulatory signal, resulting in T cell anergy. CTLA-4 in regulatory T cells (Tregs) could also function in a cell-extrinsic fashion by removing CD80/CD86 from the antigen-presenting cells (APCs), thus preventing further priming of other T cells. In this study, we examined the role of CTLA-4 in CD4+ T cell subsets from pancreatic cancer patients. In circulating CD4+ T cells, the expression of CTLA-4 was low at baseline but was significantly upregulated following T cell stimulation. Interestingly, the CTLA-4-expressing CD4+ T cells at baseline were overwhelmingly FOXP3-expressing. With the increase of T cell stimulation, the proportion of ROR gamma t-expressing CD4+ T cells was progressively increased. By CD25 vs. CCR6 staining, the CD25+CCR6+ and the CD25+CCR6- CD4+ T cells both presented high levels of CTLA-4 expression, but only the CD25+CCR6+ and the CD25-CCR6+ expressed significant amounts of IL-17. When incubated with autologous CD8+ T cells, the CD25+CCR6+ Th17 cells presented significantly higher suppressive function than the CD25-CCR6+ Th17 cells in a CTLA-4-dependent manner. Finally, the CTLA-4-expressing Th17 cells were present at higher levels in the tumor-infiltrating lymphocytes than in circulating blood. Overall, these data suggest that CTLA-4 expressing Th17 cells may present regulatory activities in pancreatic cancer patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Linfócitos T CD8-Positivos
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Carcinoma Ductal Pancreático
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Subunidade alfa de Receptor de Interleucina-2
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Células Th17
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Antígeno CTLA-4
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Tolerância Imunológica
Limite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2017
Tipo de documento:
Article