Generation of mature dendritic cells from a CD14+ cell line (XS52) by IL-4, TNF-alpha, IL-1 beta, and agonistic anti-CD40 monoclonal antibody.
We established a model system to generate mature dendritic cells (DC) from a GM-CSF-dependent cell line, XS52, which had been isolated from the epidermis of newborn BALB/c mice. Screening of various soluble factors revealed that IL-4 induces phenotypic maturation of XS52 (as evaluated by enhanced expression of class II, CD40, CD80, CD86, CD11c, and loss of expression of CD14) in a time-dependent manner. The addition of TNF-alpha, IL-1 beta, and agonistic anti-CD40 mAb further enhanced expression of these maturation markers. Consistent with their phenotypic maturation, these cells (termed XS-DC) exhibited potent Ag-presenting capacity to both naive and primed T cells. In addition, injection of hapten-conjugated XS-DC induced contact hypersensitivity in vivo, suggesting their potential as tools for vaccination. Expression of CD14 by the starting cell population, the requirement for GM-CSF and IL-4, and the relatively long culture period are the common characteristics shared between our cells and human monocyte-derived DC, whose analogues in mice have not been identified. Because large numbers of skin-associated mature DC devoid of other cell lineages are easily obtained, this model system may facilitate the study of molecular events associated with maturation of DC and the use of DC for immunization.
Yamada
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Dermatology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Katz
S I
SI
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis; D019013:CD40 Antigens / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000637:transplantation; D003877:Dermatitis, Contact / Q000209:etiology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D007375:Interleukin-1 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D007801:Langerhans Cells / Q000166:cytology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D019013:CD40 Antigens; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4