Different cytokines regulate antigen uptake and presentation of a precursor dendritic cell line.
Langerhans cells (LC) and dendritic cells (DC) need to be activated in order to perform their antigen-presenting function. In this study, we explored the influence of cytokines on the uptake and presentation of protein antigens by the retrovirally immortalized myeloid cell line FSDC. This cell line was generated from mouse fetal skin and was previously shown to have the characteristics of early DC precursors. Both FSDC and bone marrow-derived DC (BM-DC) were more effective in the pinocytosis of FITC-conjugated ovalbumin (FITC-OVA) and dextran (FITC-DX) than B cells or macrophages. Pretreatment of FSDC with granulocyte/macrophage colony-stimulating factor (GM-CSF) +/- interleukin (IL)-4 enhanced the pinocytic uptake of FITC-OVA and FITC-DX, but did not induce antigen-presenting capacity. In contrast, untreated FSDC or FSDC pre-incubated with GM-CSF +/- IL-4 suppressed T cell responses. Treatment of FSDC with IFN-gamma reduced pinocytosis but increased the expression of MHC and co-stimulatory/adhesion molecules and promoted efficient presentation of OVA protein or peptide to the specific DO11.10 T cell hybridoma or to naive CD4+ T cells from DO11.10 TCR-transgenic mice. The results suggest that antigen uptake and antigen presentation in DC are regulated by different cytokine signals provided by the surrounding tissue.
Lutz
M B
MB
CNR Center of Cytopharmacology, University of Milan, Italy.
Assmann
C U
CU
Girolomoni
G
G
Ricciardi-Castagnoli
P
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001853:Bone Marrow / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D003911:Dextrans / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008351:Mannans / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000037:antagonists & inhibitors / Q000378:metabolism; D010873:Pinocytosis / Q000187:drug effects / Q000276:immunology; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015815:Cell Adhesion Molecules; D016207:Cytokines; D003911:Dextrans; D008351:Mannans; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin; D016650:Fluorescein-5-isothiocyanate