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Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA-B27-transgenic rat model of spondylarthropathy.
- Source :
-
Arthritis and rheumatism [Arthritis Rheum] 2004 May; Vol. 50 (5), pp. 1624-35. - Publication Year :
- 2004
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Animals, Genetically Modified
Chronic Disease
Dendritic Cells immunology
Disease Models, Animal
Female
Flow Cytometry
HLA-B7 Antigen genetics
HLA-B7 Antigen immunology
Immunophenotyping
Male
Rats
Rats, Inbred BN
Rats, Inbred F344
Rats, Inbred Lew
T-Lymphocytes immunology
Antigen-Presenting Cells immunology
HLA-B27 Antigen genetics
HLA-B27 Antigen immunology
Spondylarthropathies immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0004-3591
- Volume :
- 50
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Arthritis and rheumatism
- Publication Type :
- Academic Journal
- Accession number :
- 15146433
- Full Text :
- https://doi.org/10.1002/art.20211