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, IL-1ß, and Agonistic Anti-CD40 Monoclonal Antibody
Dermatology Branch, National Cancer Institute, Bethesda, MD 20892
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-
, IL-1ß, 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.
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