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Impaired T-cell stimulation by antigen-presenting cells results from defective accessory cell function in HLA-B27 transgenic rat
Arthritis Res Ther volume 5, Article number: 69 (2003)
HLA-B27/hb2-microglobulin transgenic rats spontaneously develop a multisystem inflammatory disease resembling the human spondyloarthropathies. This disease in rats is dependent on the presence of a bacterial flora and mediated by T cells, but antigen-presenting cells (APCs) may also play a critical role. Splenic dendritic cells (DCs) have been reported to be defective in allogeneic mlR in this model.
Here, we investigated the functional defect of APCs. We observed a defective stimulation of allogeneic and syngeneic CD4+, and CD8+ LN T lymphocytes, by DC and B cells, from disease-prone 33–3 HLA-B27 transgenic, but not from healthy homozygous 120–4 HLA-B7 transgenic rats, even if stimulation was driven in the presence of Con A or anti-TCR mAbs. Pretreatment of HLA-B27 DCs with lipopolysaccharide or IFN-γ did not enhance their stimulatory capacity. In competitive culture, and transwell assay, we found no evidence for an inhibitory factor or a lack of diffusible factor produced by HLA-B27 DCs. When comparing class II MHC, CD2, B7, ICAM1, and LFA-1 molecules at the surface of DC from 33–3, 120–4, and nontransgenic rats, we found no difference. However, the proportion of conjugates formed between 33–3 DC and allogeneic or syngeneic T cells was decreased, which could account for a defective stimulation of those T cells. We have confirmed a defective stimulation of T cells by APCs in disease-prone 33–3 rats, the mechanism of which appears to implicate APC/T-cell contact, independently of TCR engagement. It must involve accessory cell function, and could explain a loss of tolerance towards microbial flora in this model of spondyloarthropathy.
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Falgarone, G., Hacquard-Bouder, C., Bosquet, A. et al. Impaired T-cell stimulation by antigen-presenting cells results from defective accessory cell function in HLA-B27 transgenic rat. Arthritis Res Ther 5, 69 (2003). https://doi.org/10.1186/ar699
- Bacterial Flora
- Transwell Assay
- Microbial Flora
- Diffusible Factor