The signals controlling the checkpoints of dendritic cells (DC) maturation and the correlation between phenotypical and functional maturational stages were investigated in a defined model system of growth factor–dependent immature mouse DC. Three sequential stages of DC maturation (immature, mature, and apoptotic) were defined and characterized. Immature DC (stage 1) had low expression of costimulatory molecules, highly organized cytoskeleton, focal adhesion plaques, and slow motility; accordingly, they were very efficient in antigen uptake and processing of soluble proteins. Further, at this stage most of major histocompatibility complex class II molecules were within cytoplasmic compartments consistent with a poor allostimulatory capacity. Bacteria or cytokines were very efficient in inducing progression from stage 1 towards stage 2 (mature). Morphological changes were observed by confocal analysis including depolymerization of F-actin and loss of vinculin containing adhesive structures which correlates with acquisition of high motility. Antigen uptake and presentation of native protein antigen was reduced. In contrast, presentation of immunogenic peptides and allostimulatory activity became very efficient and secretion of IL-12 p75 was detectable after antigen presentation. This functional DC maturation ended by apoptotic cell death, and no reversion to the immature phenotype was observed.
Dendritic cells (DC) are professional antigen‐presenting cells (APC) whose primary function is to capture, process, and present antigens to unprimed T cells [1, 2]. They comprise a system of leukocytes widely distributed in all tissues, especially in those that provide an environmental interface (skin and mucosal surfaces) and in lymphoid organs [1].
A number of apoptotic stimuli produce a different response by CD4 1 regulatory and effector lymphocytes. So far, little is known concerning the sensitivity of CD4 1 regulatory T cells (Treg) to genotoxic agents. Observations from a mouse model suggest that Treg are more resistant to DNA damage compared to CD4
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