Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA–B27–transgenic rat model of spondylarthropathy
✍ Scribed by Cécile Hacquard-Bouder; Géraldine Falgarone; Antoine Bosquet; Faïza Smaoui; Dominique Monnet; Marc Ittah; Maxime Breban
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 177 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
Abstract
Objective
A disease resembling the human spondylarthropathies develops in HLA–B27–transgenic rats. This disease in rats is mediated by CD4+ T cells, but antigen‐presenting cells (APCs) may also play a role. Dendritic cells (DCs) have been reported to be defective in allogeneic mixed lymphocyte culture in this model. Here, we further investigated the functional defect of APCs.
Methods
DCs and B cells from nontransgenic, HLA–B27 (33–3)–transgenic, and HLA–B7 (120–4)–transgenic rats were used to stimulate T cells. Surface expression of HLA–B transgene and rat molecules on APCs and the formation of conjugates between DCs and T cells were monitored by flow cytometry.
Results
We observed a strikingly defective stimulation of allogeneic and syngeneic T lymphocytes by APCs from HLA–B27 but not HLA–B7 rats, even if stimulation was driven in the presence of anti–T cell receptor (TCR) antibody. We found no evidence that HLA–B27 DCs were immature, lacked production of some diffusible factor, or produced an inhibitory factor for T cells. When comparing the levels of expression of class II major histocompatibility complex, CD2, intercellular adhesion molecule 1, lymphocyte function–associated antigen 1, B7, and CD40 molecules at the surface of DCs from 33‐3, 120‐4, and nontransgenic rats, we found little difference. However, HLA–B27–transgenic DCs formed fewer conjugates with T cells than did nontransgenic DCs. Furthermore, the proportion of conjugates formed between DCs and T cells, as well as the difference between nontransgenic and HLA–B27–transgenic DCs, were in large part reduced by blocking CD86 on DCs.
Conclusion
We confirmed defective stimulation of T cells by APCs in HLA–B27 rats, the mechanism of which appears to implicate APC/T cell contact, independent of TCR engagement. In addition, decreased use of the CD86 costimulatory molecule by B27 DCs was observed. Impaired costimulatory function could result in a loss of tolerance toward microbial flora in this model.