Ifn-α and il-10 induce the differentiation of human type 1 t regulatory cells1

M. K. Levings, R. Sangregorio, F. Galbiati, S. Squadrone, R. De Waal Malefyt, M. G. Roncarolo

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)5530-5539
Number of pages10
JournalJournal of Immunology
Volume166
Issue number9
Publication statusPublished - May 1 2001

ASJC Scopus subject areas

  • Immunology

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