Biology Reference
In-Depth Information
F i g u r e 11.2. The di¨erent stages of the DC life cycle are mediated by cytokines in vitro. Imma-
ture DC are cultured in vitro from monocytes or CD34
progenitors in the presence of cytokines,
maturation is induced by CD40 ligation, the bacterial cell-wall component lipopolysaccharide
(LPS ) or tumor necrosis factor-a (TNF-a). Immature and mature DC have di¨erent distinct char-
acteristics, which are required for their specialized functions.
stimulating T cells. Conversely, the mature form is equipped with an extremely
e½cient antigen-presenting machinery, but is poor at uptake and processing
( Fig. 11.2). Immature and mature DC speci®cally migrate to those sites where
they can perform their functions optimally. Stimulatory cytokines released at
sites of in¯ammation induce the immature DC to mature and migrate speci®-
cally to lymphoid tissues through the a¨erent lymph. Phagocytic and antigen-
processing activities are down-regulated during maturation, and the expression
of costimulatory and adhesion molecules involved in e½cient antigen presenta-
tion to T cells are up-regulated. Therefore, DC transport an antigenic repre-
sentation of the invading pathogen to the T-cell areas of lymphoid tissues,
where they are ideally positioned to interact with many naive T cells and acti-
vate those that are antigen-speci®c. The peptide-MHC complexes are extremely
stable, enabling a thorough screening by T cells.
MOLECULAR MAKE-UP OF IMMATURE AND MATURE DENDRITIC
CELLS
The elucidation of methods of culturing DC in vitro at a de®ned maturation
state from either monocytes or bone marrow progenitors in the presence of cyto-
