IL-10 stimulates monocyte Fc gamma R surface expression and cytotoxic activity. Distinct regulation of antibody-dependent cellular cytotoxicity by IFN-gamma, IL-4, and IL-10.
T cell-derived cytokines IFN-gamma and IL-4 have different regulatory effects on two functionally important molecules on human monocytes: MHC class II Ag and the Fc receptor for monomeric IgG, Fc gamma RI (CD64). MHC class II Ag, and Fc gamma RI are both upregulated in the presence of IFN-gamma. IL-4 induces MHC class II Ag expression but reduces Fc gamma RI expression. Recently, we showed that the cytokine IL-10 also affects MHC class II Ag expression. Here, we demonstrate that in contrast to the down-regulation of MHC class II Ag expression, IL-10 stimulates Fc gamma RI expression on human monocytes comparable to the levels of Fc gamma RI expression induced by IFN-gamma. The IL-10-induced Fc gamma RI expression is specific because anti-IL-10 antibodies completely reverse the IL-10-induced surface expression of Fc gamma RI and correlate with an enhanced capacity to lyse anti-D-coated human rhesus-positive erythrocytes. IL-10 fails to induce the expression of Fc gamma RII (CD32) and Fc gamma RIII (CD16). Furthermore, we demonstrate that IL-10 is able to prevent down-regulation in surface membrane expression of all three Fc gamma R that can be found when monocytes are cultured in the presence of IL-4. In contrast to IFN-gamma, IL-10 does not restore the reduced antibody-dependent cellular cytotoxicity (ADCC) activity of IL-4-cultured monocytes. Together, these results show that, similar to IFN-gamma, IL-10 is capable of enhancing Fc gamma R expression and ADCC activity, and that IFN-gamma, IL-4, and IL-10 have different regulatory effects on both monocyte Ag-presenting capacity and ADCC activity.
te Velde
A A
AA
Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
de Waal Malefijt
R
R
Huijbens
R J
RJ
de Vries
J E
JE
Figdor
C G
CG
D000920:Antibody-Dependent Cell Cytotoxicity; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000276:immunology*; D015847:Interleukin-4 / Q000502:physiology; D009000:Monocytes / Q000378:metabolism*; D017452:Receptors, IgG / Q000096:biosynthesis*; D015854:Up-Regulation / Q000276:immunology*
D017452:Receptors, IgG; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma