Are interleukin-16 and thrombopoietin new tools for the in vitro generation of dendritic cells?
The effects of interleukin 16 (IL-16) on dendritic cell (DC) generation from human CD34(+) progenitor cells are not known. Here, we show that IL-16 added to a basal cocktail comprised of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, Flt-3 ligand (Flt3L), and tumor necrosis factor alpha (TNF-alpha) does induce the CD34(+) hematopoietic cells to proliferate in vitro and to differentiate into phenotypically and functionally mature DCs. IL-16 exerts this function more efficiently than stem cell factor (SCF) as a control, thrombopoietin (TPO), or IL-16 plus TPO. Moreover, we show that the combination of IL-16 plus TPO induces the generation of tolerogenic DCs, able to induce an anergic state in T cells that persists when T cells are rechallenged with immunogenic DCs. An altered pattern of cytokine production, a reduced expression of the C-type lectin DC-SIGN, and an increased surface expression of the inhibitory molecules immunoglobulin-like transcript 2 (ILT-2), ILT-3, and ILT-4 may all contribute to confer the tolerogenic properties of these DCs. Generation of tolerogenic DCs may aid the exploration of new therapeutic strategies to promote tolerance to autoantigens and prevent disease development.
Dipartimento di Scienze e Tecnologie Biomediche, Laboratorio di Immunologia, Università di Milano, Italy.
Silvia
S
Della Bella
Stefania
S
Nicola
Inna
I
Timofeeva
Maria Luisa
ML
Villa
Armando
A
Santoro
Anna C
AC
Berardi
D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D018929:Cell Culture Techniques / Q000379:methods; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004705:Endocytosis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D019410:Interleukin-16 / Q000276:immunology*; D037181:Lectins, C-Type / Q000502:physiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D013926:Thrombopoietin / Q000276:immunology*
D015703:Antigens, CD; D018952:Antigens, CD34; D019410:Interleukin-16; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D013926:Thrombopoietin