Dendritic cells lose ability to present protein antigen after stimulating antigen-specific T cell responses, despite upregulation of MHC class II expression.
Immature dendritic cells (DC) take up, process and present protein antigens; mature DC are specialized for stimulating primary T cell responses with increased expression of MHC class II and co-stimulatory molecules, but are incapable of processing and presenting soluble protein. The current study examined whether maturation of DC is triggered by T cell recognition of antigens presented by immature DC. Human DC derived from CD34+ progenitor cells by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) in serum-free medium could prime naive CD4+ T cells to keyhole limpet hemocyanin (KLH) and ovalbumin (OVA). The cultured DC retained the ability to prime T cells to native protein for at least 15 days. To test for changes in DC function after participation in an immune response, DC were co-cultured with either allogeneic or autologous CD4+ T cells. DC co-cultured with autologous T cells retained the ability to prime T cells to intact protein antigens. By contrast, DC which had previously stimulated an allogeneic T cell response lost ability to prime T cells to soluble proteins. However, such <<T cell-activated DC>> induced a MLR and stimulated peptide-specific primary CD4+ T cell responses. This indicated that <<T cell-activated DC>> did not die or lose the ability to prime, but lost the ability to process and present subsequent antigens. Following participation in T cell activation, DC increased surface expression of MHC class II, co-stimulatory molecules CD40 and B7.2, and the intercellular adhesion molecule-1 (ICAM-1). In addition, our data suggest that interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are involved in this T cell-mediated DC maturation.
Bernhard
H
H
1. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, Germany. helga.bernhard@lrz.tum.de
Huseby
E S
ES
Hand
S L
SL
Lohmann
M
M
Batten
W Y
WY
Disis
M L
ML
Gralow
J R
JR
Meyer zum Büschenfelde
K H
KH
Ohlén
C
C
Cheever
M A
MA
D017951:Antigen Presentation / Q000276:immunology; D018122:B7-1 Antigen / Q000032:analysis; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000032:analysis; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016895:Culture Media, Serum-Free; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006433:Hemocyanins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018122:B7-1 Antigen; D019013:CD40 Antigens; D016895:Culture Media, Serum-Free; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin