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IFN-α and IL-10 Induce the Differentiation of Human Type 1 T Regulatory Cells
Abstract
CD4+ T regulatory type 1 (Tr1) cells suppress Ag-specific immune responses in vitro and in vivo. Although IL-10 is critical for the differentiation of Tr1 cells, the effects of other cytokines on differentiation of naive T cells into Tr1 cells have not been investigated. Here we demonstrate that endogenous or exogenous IL-10 in combination with IFN-α, but not TGF-β, induces naive CD4+ T cells derived from cord blood to differentiate into Tr1 cells: IL-10+IFN-γ+IL-2−/lowIL-4−. Naive CD4+ T cells derived from peripheral blood require both exogenous IL-10 and IFN-α for Tr1 cell differentiation. The proliferative responses of the Tr1-containing lymphocyte populations, following activation with anti-CD3 and anti-CD28 mAbs, were reduced. Similarly, cultures containing Tr1 cells displayed reduced responses to alloantigens via a mechanism that was partially mediated by IL-10 and TGF-β. More importantly, Tr1-containing populations strongly suppressed responses of naive T cells to alloantigens. Collectively, these results show that IFN-α strongly enhances IL-10-induced differentiation of functional Tr1 cells, which represents a first major step in establishing specific culture conditions to generate T regulatory cells for biological and biochemical analysis, and for cellular therapy to induce peripheral tolerance in humans.
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Metadata
- Authors
- Levings, M. K., Sangregorio, R., Galbiati, F., Squadrone, S., de Waal Malefyt, R., & Roncarolo, M.-G.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-05-01
- Volume
- 166
- Issue
- 9
- Pages
- 5530-5539
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2136245823
- Cited by
- 595
- References
- 1
- FWCI
- 11.94
- Type
- journal article
- Language
- en
- Open access
- closed
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