Human antigen-specific CD4⺠CD25⺠CD134⺠CD39⺠T cells are enriched for regulatory T cells and comprise a substantial proportion of recall responses.
Eur J Immunol
; 44(6): 1644-61, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24752698
ABSTRACT
Human Ag-specific CD4(+) T cells can be detected by their dual expression of CD134 (OX40) and CD25 after a 44 hours stimulation with cognate Ag. We show that surface expression of CD39 on Ag-specific cells consistently identifies a substantial population of CD4(+) CD25(+) CD134(+) CD39(+) T cells that have a Treg-cell-like phenotype and mostly originate from bulk memory CD4(+) CD45RO(+) CD127(low) CD25(high) CD39(+) Treg cells. Viable, Ag-specific CD25(+) CD134(+) CD39(+) T cells could be expanded in vitro as cell lines and clones, and retained high Forkhead Box Protein 3, CTLA-4 and CD39 expression, suppressive activity and Ag specificity. We also utilised this combination of cell surface markers to measure HIV-Gag responses in HIV(+) patients before and after anti-retroviral therapy (ART). Interestingly, we found that the percentage of CD39(-) cells within baseline CD4(+) T-cell responses to HIV-Gag was negatively correlated with HIV viral load pre-ART and positively correlated with CD4(+) T-cell recovery over 96 weeks of ART. Collectively, our data show that Ag-specific CD4(+) CD25(+) CD134(+) CD39(+) T cells are highly enriched for Treg cells, form a large component of recall responses and maintain a Treg-cell-like phenotype upon in vitro expansion. Identification and isolation of these cells enables the role of Treg cells in memory responses to be further defined and provides a development pathway for novel therapeutics.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apirase
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Antígenos CD
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Antígenos CD4
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Infecções por HIV
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HIV-1
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Proteína do Núcleo p24 do HIV
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Linfócitos T Reguladores
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Subunidade alfa de Receptor de Interleucina-2
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Receptores OX40
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Antígenos Virais
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Austrália