IL-6 produced by type I IFN DC controls IFN-gamma production by regulating the suppressive effect of CD4+ CD25+ regulatory T cells.
The dendritic cell family is composed of different subsets differentially governing the immune response. Type I interferon (IFN) dendritic cells (DC) are endowed with the ability to trigger both Th1 and Th2 type responses. In view of the pivotal role of regulatory T cells in limiting the effectiveness of effector cells, we analyzed the interactions between these cells and type I IFN DC. DC were generated from monocytes in the presence of IFN-beta and interleukin (IL)-3 (DCI3) or granulocyte macrophage-colony-stimulating factor and IL-4 (DCG4) and activated by poly(I:C). Despite the release of lower amounts of IL-12 after maturation, DCI3 were able to induce a higher IFN-gamma production by T lymphocytes during the mixed leucocyte reaction (MLR) as compared with DCG4. mRNA analysis disclosed that DCI3 overtranscribed the IL-6 gene and secreted high amounts of the protein. Neutralization of IL-6 revealed that this cytokine specifically contributed to the IFN-gamma release induced by DCI3. Finally, depletion of CD25+ T cells before the MLR identified these cells as a target for IL-6. We conclude that DCI3 are endowed with the property of regulating the suppressive effect of regulatory T cells through high IL-6 production. This novel mechanism of T cell control is relevant for the use of DCI3 in vaccination strategies.
Detournay
Olivier
O
Department of Immunology-Hematology-Transfusion, Erasme Hospital, Brussels, Belgium.
Mazouz
Naima
N
Goldman
Michel
M
Toungouz
Michel
M
D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D011070:Poly I-C / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000906:Antibodies; D015703:Antigens, CD; D016207:Cytokines; D007370:Interferon Type I; D016898:Interferon-alpha; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D021122:Protein Subunits; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma; D011070:Poly I-C