TY - JOUR
T1 - Ifn-α and il-10 induce the differentiation of human type 1 t regulatory cells1
AU - Levings, M. K.
AU - Sangregorio, R.
AU - Galbiati, F.
AU - Squadrone, S.
AU - De Waal Malefyt, R.
AU - Roncarolo, M. G.
PY - 2001/5/1
Y1 - 2001/5/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 11313392
AN - SCOPUS:0035339884
VL - 166
SP - 5530
EP - 5539
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -