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Split activity of interleukin‐10 on antigen capture and antigen presentation by human dendritic cells: Definition of a maturative step

Human CD1+ CD14‐ dendritic cells (DC) can be derived from CD14+ monocytes using granulocyte/monocyte colony‐stimulating factor and interleukin (IL)‐4. We have previously shown that IL‐10 pre‐treatment of such DC significantly inhibited their antigen‐presenting capacity to CD4+ T cell clones. In this study, we further analyze how IL‐10 influences antigen presentation. We first investigated whether IL‐10 could alter the early stage of antigen presentation, the capture of antigen. This can be mediated by mannose receptor (MR)‐mediated endocytosis and by fluid‐phase uptake through macropinocytosis. IL‐10‐treated DC showed an enhancement of both mechanisms of antigen capture, as indicated by the increase of fluorescein isothiocyanate‐dextran uptake through MR and lucifer yellow uptake. However, IL‐10‐treated DC, irradiated or glutaraldehyde‐fixed, were less efficient than untreated DC in stimulating mixed leukocyte reaction as well as in inducing the activation of peptide‐specific T cell clones, indicating that IL‐10 achieves its effects mainly by modifying the cell surface phenotype of DC. HLA class I and II, as well as intercellular adhesion molecule (ICAM)‐1, lymphocyte function‐associated antigen‐3, B7‐1, B7‐2 and ICAM‐3 expression were either significantly increased or essentially unchanged, and the ability to bind the epitope recognized by the T cell clones was also unaffected regardless of IL‐10 treatment. Our study also indicates that as‐yet unidentified accessory molecules may play an essential role in T cell activation. Thus, the IL‐10‐treated DC possess an increased capacity to capture antigen, with a concomitant decreased stimulatory activity. Our study suggests that IL‐10‐treated DC have the characteristics of highly immature DC (high capture ability, low stimulatory potency) and may represent an early maturative step of human DC of monocytic origin.