Alteration of antigen-independent immunologic synapse formation between dendritic cells from HLA–B27–transgenic rats and CD4+ T cells: Selective impairment of costimulatory molecule engagement by mature HLA–B27
✍ Scribed by Cécile Hacquard-Bouder; Maria-Sole Chimenti; Benoît Giquel; Emmanuel Donnadieu; Ingrid Fert; Alain Schmitt; Claudine André; Maxime Breban
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 417 KB
- Volume
- 56
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Objective
To investigate the molecular mechanism responsible for the reduced capacity of dendritic cells (DCs) from HLA–B27–transgenic rats to form conjugates with naive T cells.
Methods
We monitored interactions between DCs derived from HLA–B27–transgenic, HLA–B7–transgenic control, and nontransgenic rats and naive CD4+ T cells. Chemoattraction was studied in Transwell assays, and the formation of an immunologic synapse was examined by videomicroscopy and electron microscopy. Involvement of specific molecules in the defective interaction was examined in antibody‐blocking assays.
Results
T cells migrated normally toward B27 DCs, but upon contact, the frequency of T cells undergoing a Ca^2+^ response was decreased, indicating impaired immunologic synapse formation. The immunologic synapse formed between B27 DCs and T cells appeared to be normal, as assessed by electron microscopy and by the Ca^2+^ response. Blocking lymphocyte function−associated antigen 1 on T cells or blocking activated leukocyte cell adhesion molecules on DCs inhibited an equivalent proportion of conjugates from forming between B27 or control DCs and T cells, whereas blocking CD86 on DCs and blocking CD28, CD2, or CD4 on T cells inhibited a greater number of conjugates from forming with control DCs, indicating specific involvement of costimulatory molecules in the reduced formation of conjugates with B27 DCs. Mature B27 molecules on the DC surface were responsible for this decreased formation of conjugates.
Conclusion
In the HLA–B27–transgenic rat model of spondylarthropathy, mature B27 molecules expressed by DCs impair the formation of an antigen‐independent immunologic synapse with naive CD4+ T cells by interfering with the engagement of costimulatory molecules. This phenomenon could potentially affect the production and/or maintenance of regulatory T cells and contribute to the expansion of pathogenic CD4+ T cells.