Efficient Presentation of Soluble Antigen by Cultured Human Dendritic Cells Is Maintained by Granulocyte/Macrophage Colony-stimulating Factor Plus Interleukin 4 and Downregulated by Tumor Necrosis Factor α

被引:4427
作者
Sallusto, Federica [1 ,2 ]
Lanzavecchia, Antonio [1 ]
机构
[1] Basel Inst Immunol, Grenzazcherstr 487, CH-4005 Basel, Switzerland
[2] Ist Super Sanita, Dept Immunol, I-00161 Rome, Italy
关键词
EPIDERMAL LANGERHANS CELLS; CD4+ T-CELLS; PRESENTING CELLS; IN-VITRO; IMMUNOLOGICAL-PROPERTIES; PROLIFERATIVE RESPONSES; PROTEIN ANTIGENS; B-CELLS; EXPRESSION; GENERATION;
D O I
10.1084/jem.179.4.1109
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 we have established dendritic cell (DC) lines from blood mononuclear cells that maintain the antigen capturing and processing capacity characteristic of immature dendritic cells in vivo. These cells have typical dendritic morphology, express high levels of major histocompatibility complex (MHC) class I and class II molecules, CD1, Fc gamma RII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured DCs are highly stimulatory in mixed leukocyte reaction (MLR) and are also capable of triggering cord blood naive T cells. Most strikingly, these DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones. Their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR-mediated antigen uptake. Incubation of these cultured DCs with tumor necrosis factor alpha (TNF-alpha) or soluble CD40 ligand (CD40L) for 24 h results in an increased surface expression of MHC class I and class II molecules, B7, and ICAM-1 and in the appearance of the CD44 exon 9 splice variant (CD44-v9); by contrast, Fc gamma RII is markedly and sometimes completely downregulated. The functional consequences of the short contact with TNF-alpha are in increased T cell stimulatory capacity in MLR, but a 10-fold decrease in presentation of soluble TT and a 100-fold decrease in presentation of TT-immunoglobulin G complexes.
引用
收藏
页码:887 / 896
页数:10
相关论文
共 48 条
[1]  
AIBA S, 1991, J IMMUNOL, V146, P2479
[2]  
Austyn J M, 1992, Semin Immunol, V4, P227
[3]   MIGRATION PATTERNS OF DENDRITIC LEUKOCYTES - IMPLICATIONS FOR TRANSPLANTATION [J].
AUSTYN, JM ;
LARSEN, CP .
TRANSPLANTATION, 1990, 49 (01) :1-7
[4]   INTERCONVERSION OF CD45R SUBSETS OF CD4 T-CELLS INVIVO [J].
BELL, EB ;
SPARSHOTT, SM .
NATURE, 1990, 348 (6297) :163-166
[5]   GM-CSF AND TNF-ALPHA COOPERATE IN THE GENERATION OF DENDRITIC LANGERHANS CELLS [J].
CAUX, C ;
DEZUTTERDAMBUYANT, C ;
SCHMITT, D ;
BANCHEREAU, J .
NATURE, 1992, 360 (6401) :258-261
[6]   RESPONSE OF NAIVE ANTIGEN-SPECIFIC CD4+ T-CELLS INVITRO - CHARACTERISTICS AND ANTIGEN-PRESENTING CELL REQUIREMENTS [J].
CROFT, M ;
DUNCAN, DD ;
SWAIN, SL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (05) :1431-1437
[7]  
CUMBERBATCH M, 1992, IMMUNOLOGY, V75, P257
[8]   PROCESSING AND PRESENTATION OF INTACT HEN EGG-WHITE LYSOZYME BY DENDRITIC CELLS [J].
DEBRUIJN, MLH ;
NIELAND, JD ;
HARDING, CV ;
MELIEF, CJM .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (09) :2347-2352
[9]   THE MINIMAL NUMBER OF CLASS-II MHC ANTIGEN COMPLEXES NEEDED FOR T-CELL ACTIVATION [J].
DEMOTZ, S ;
GREY, HM ;
SETTE, A .
SCIENCE, 1990, 249 (4972) :1028-1030
[10]   THE DISTINCT SURFACE OF HUMAN BLOOD DENDRITIC CELLS, AS OBSERVED AFTER AN IMPROVED ISOLATION METHOD [J].
FREUDENTHAL, PS ;
STEINMAN, RM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (19) :7698-7702