Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA-B27-transgenic rat model of spondylarthropathy.
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.


CONCLUSIONS
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.
Hacquard-Bouder
Cécile
C
Cochin Hospital, INSERM, CNRS, Université René Descartes, Paris, France.
Falgarone
Géraldine
G
Bosquet
Antoine
A
Smaoui
Faïza
F
Monnet
Dominique
D
Ittah
Marc
M
Breban
Maxime
M
D000818:Animals; D030801:Animals, Genetically Modified; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology*; D015793:HLA-B7 Antigen / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D025242:Spondylarthropathies / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D015796:HLA-B27 Antigen; D015793:HLA-B7 Antigen