Rapamycin combined with TGF-ß converts human invariant NKT cells into suppressive Foxp3+ regulatory cells.
J Immunol
; 188(2): 624-31, 2012 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-22156591
ABSTRACT
Invariant NKT (iNKT) cells constitute a versatile T cell subset with important regulatory functions, which are thought to result essentially from their capacity to promptly produce cytokines that influence the Th1/Th2 balance. In this study, we report that these cells can also express Foxp3, an important transcriptional regulator associated with suppressive activity, once they have been exposed to TGF-ß. Foxp3 was expressed by iNKT cells from both peripheral and cord blood. CD4(+) iNKT cells acquired Foxp3 expression preferentially, although a lower proportion of their CD4(-) counterpart also became positive. All Foxp3(+) iNKT cells displayed CD25 but not necessarily CTLA4 or GITR, regardless of the upregulation of these markers in the presence of TGF-ß. Exposure to TGF-ß decreased IL-4 and IFN-γ production while increasing IL-10, independently from Foxp3 expression. IL-17 was not detected. TGF-ß induced high levels of Foxp3, but no suppressor activity, which emerged only in the presence of rapamycin. Peripheral and cord blood Foxp3(+) iNKT cells suppressed the proliferation of conventional autologous and heterologous CD4(+) T cells equally, in a cell contact-dependent and Ag-independent manner. Our findings demonstrate that human iNKT cells become suppressive in the presence of TGF-ß plus rapamycin, thus adding a new facet to their complex functional properties.
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Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Fator de Crescimento Transformador beta
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Linfócitos T Reguladores
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Sirolimo
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Fatores de Transcrição Forkhead
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Células T Matadoras Naturais
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Imunossupressores
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article