Related Experiment Video
Updated: Jul 18, 2026
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Relevance of DC-SIGN in DC-induced T cell proliferation
Karlijn Gijzen1, Paul J Tacken, Aukje Zimmerman
1Department of Tumor Immunology, NCMLS 278, Radboud University Nijmegen Medical Centre, Geert Grooteplein 26/28, 6525 GA Nijmegen, The Netherlands.
Insights
Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) plays a brief, early role in T cell activation. Its impact on T cell proliferation is most noticeable with low proliferation rates and high DC-SIGN binding capacity.
Area of Science:
- Immunology
- Cell Biology
Background:
- Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a C-type lectin receptor expressed on dendritic cells.
- DC-SIGN is implicated in cell-cell adhesion and immune regulation, particularly in DC-T cell interactions.
Purpose of the Study:
- To investigate the precise role and kinetics of DC-SIGN in dendritic cell (DC)-T cell communication.
- To determine how DC-SIGN function is influenced by the magnitude of mixed lymphocyte reaction (MLR) and DC maturation status.
Main Methods:
- Mixed lymphocyte reaction (MLR) assays were performed using DC-SIGN-blocking monoclonal antibodies (mAbs).
- The effect of mAb addition at various time points during MLR was analyzed.
- The percentage of peripheral blood lymphocytes (PBL) capable of binding to DC-SIGN was quantified using recombinant DC-SIGN-coated beads.
Main Results:
- DC-SIGN and LFA-1 blockade inhibited MLR, with inhibition levels dependent on MLR magnitude and DC maturation.
- DC-SIGN blockade early in MLR indicated an initial role in DC-T cell contacts, transiently masked by other mechanisms.
- 1-20% of PBL from various donors bound to DC-SIGN, encompassing all major blood cell subsets.
- PBL with high DC-SIGN binding capacity showed greater MLR inhibition upon DC-SIGN blockade.
Conclusions:
- DC-SIGN plays an initial, transient role in T cell proliferation during DC-T cell interactions.
- This transient role is more apparent under conditions of low T cell proliferation and high DC-SIGN binding capacity of PBL.
Abstract:
The role of dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in DC-T cell communication was assessed by analyzing the effect of DC-SIGN-blocking mAb in MLR. The results show that the degree of inhibition by DC-SIGN and LFA-1 mAb depends on the magnitude of the MLR and the maturation status of the DC. Addition of DC-SIGN mAb at several time-points during MLR showed that DC-SIGN is involved early on in DC-T cell contacts. This initial role is masked by strong adhesive and costimulatory mechanisms, indicating a short-lived effect of DC-SIGN in DC-T cell interactions. To examine this concept in more detail, the percentage of PBL capable of binding DC-SIGN was determined. Analysis of several donors revealed that 1-20% PBL bind to beads coated with recombinant DC-SIGN, and the DC-SIGN-binding cells comprised all major cell subsets found in blood. PBL isolated from a donor with high DC-SIGN-binding capacity were more prone to blocking by DC-SIGN mAb in MLR than PBL from a donor with low DC-SIGN-binding capacity. This study indicates an initial and transient role for DC-SIGN in T cell proliferation, which becomes apparent when T cell proliferation is low and when the percentage of DC-SIGN binding PBL is high.
