Rapamycin Combined with TGF-beta Converts Human Invariant NKT Cells into Suppressive Foxp3(+) Regulatory Cells

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Lucia Moreira Teixeira (Author) Other; Mariana Resende (Author) Other; Odile Devergne (Author) Other; Jean Philippe Herbeuval (Author) Other; Olivier Hermine (Author) Other; Elke Schneider (Author) Other; Michel Dy (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Maria C Leite de Moraes (Author) Other

Journal

Title: Journal of Immunology

Vol. 188

Pages: 624-631

ISSN: 0022-1767

Publisher: American Association of Immunologists

Indexing

ISI Web of Knowledge - 36 Citations

Scopus - 41 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-DXA

DOI: 10.4049/jimmunol.1102281

Abstract (EN): 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-beta. 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-beta. Exposure to TGF-beta decreased IL-4 and IFN-gamma production while increasing IL-10, independently from Foxp3 expression. IL-17 was not detected. TGF-beta 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-beta plus rapamycin, thus adding a new facet to their complex functional properties. The Journal of Immunology, 2012, 188: 624-631.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8