T Lymphocyte Mediated Regulation of Costimulator Molecule Expression on Human Dendritic Cells
The potent T lymphocyte stimulatory capacity of DC and other antigen presenting cell types is not constitutive and requires an activation/maturation event that can be provided by in vitro culture or enhanced by both membrane bound and soluble factors.1–4 Culture or cytokine induced increases in DC stimulatory activity correlate with the upregulation of the CD40 and CD86 costimulatory molecules, which are essential for optimal T lymphocyte activation. Although the allostimulatory activity of fresh peripheral blood DC (fPBDC) is inhibited by antibodies or soluble recombinant constructs which block the CD86:CD28 or CD40:CD4OL interaction,1,5,6 paraformaldehyde fixed, freshly isolated DC are incapable of initiating T lymphocyte proliferation unless they are subjected to a period of culture prior to fixation.3,7 This implies that costimulatory molecules are upregulated on fresh DC during DC:T lymphocyte coculture. Studies of the kinetics of costimulation indicate that DC must provide this “second signal” in the very early stages of DC:T lymphocyte contact for full T lymphocyte activation to occur.5,8,9
KeywordsCostimulatory Signal Human Dendritic Cell CD86 Costimulatory Molecule Antigen Present Cell Function CD40L Interaction
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