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Cross-linking of membrane CD43 mediates dendritic cell maturation
S Corinti1, E Fanales-Belasio, C Albanesi
1Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
Insights
CD43 cross-linking activates dendritic cells (DCs), enhancing their maturation and T cell stimulation. This process impacts immune responses by altering DC function and antigen presentation.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD43 (leukosialin) is a key surface molecule on dendritic cells (DCs).
- CD43 regulates cell adhesion and may mediate DC activation signals.
Purpose of the Study:
- To investigate the functional consequences of CD43 cross-linking on dendritic cell (DC) activation and maturation.
- To assess the impact of CD43 ligation on DC cytokine production, antigen presentation, and T cell stimulatory capacity.
Main Methods:
- Monocyte-derived DCs were incubated with anti-CD43 monoclonal antibody (mAb) MEM-59 or its fragments.
- Analysis included cell surface marker expression (HLA-DR, CD54, CD40, CD80, CD86, CD83), cytokine release, endocytic activity, T cell proliferation assays (MLR), and intracellular signaling.
- Specific antigen presentation assays using HIV-1 reverse transcriptase and its peptide were performed.
Main Results:
- CD43 cross-linking significantly upregulated key DC activation markers (HLA-DR, CD54, CD40, CD80, CD86, CD83).
- Ligation of CD43 induced the release of pro-inflammatory and regulatory cytokines (IL-1β, IL-6, TNF-α, IL-12, IL-10).
- Anti-CD43 treatment enhanced DC capacity to stimulate T cell proliferation, inhibited endocytosis, and modulated antigen presentation efficiency.
Conclusions:
- CD43 cross-linking triggers a cascade of events leading to dendritic cell (DC) activation and functional maturation.
- These findings highlight CD43 as a critical regulator of DC function with implications for immune responses and potential therapeutic targeting.
Abstract:
CD43/leukosialin is a major sialoglycoprotein of the dendritic cell (DC) surface, which can regulate cell adhesion and has the potential to mediate cell activation signals. Monocyte-derived DC transiently incubated with the anti-CD43 mAb, MEM-59, or with F(ab')2 fragments, but not with monovalent Fab fragments or control IgG, 24 h later showed increased levels of membrane HLA-DR, CD54, CD40, CD80, CD86, and CD83. In parallel, CD43 cross-linking induced synthesis and release of IL-1beta, IL-6, TNF-alpha, IL-12, and IL-10. CD43 ligation inhibited the endocytic activity of DC, and enhanced the capacity of DC to stimulate T cell proliferation in the primary allogeneic and autologous MLR assay. In addition, anti-CD43-treated DC were less efficient at presenting native HIV-1 reverse transcriptase to a specific CD4+ T cell clone, whereas presentation of the reverse transcriptase 55-72 peptide to the same clone was increased. Finally, MEM-59 or its F(ab')2 fragments elicited a rise in intracellular free calcium and tyrosine phosphorylation of a 25-kDa protein in DC. The results thus indicate that CD43 cross-linking with specific ligands induces activation and functional maturation of DC.