Open AccessCorrelation between dendritic cell functional defect and spondylarthritis phenotypes in HLA–B27/HUMAN β 2 ‐microglobulin–transgenic rat lines
Author(s) -
Fert Ingrid,
Glatigny Simon,
Poulain Cécile,
Satumtira Nimman,
Dorris Martha L.,
Taurog Joel D.,
Breban Maxime
Publication year - 2008
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24023
Subject(s) - transgene , genetically modified mouse , beta 2 microglobulin , immunology , phenotype , hla b27 , biology , microbiology and biotechnology , human leukocyte antigen , antigen , gene , genetics
Objective To examine the functional capacity of dendritic cells (DCs) from a panel of HLA–B27/human β 2 ‐microglobulin (Huβ 2 m)–transgenic rat lines and crosses with varying susceptibilities to spondylarthritis (SpA)–like disease. Methods Mature splenic DCs were isolated from HLA–B27–transgenic, HLA–B7–transgenic, and/or Huβ 2 m‐transgenic rats and tested for support of allogeneic proliferation, compared with nontransgenic controls (all male rats on Lewis background). Graded numbers of DCs were cultured with allogeneic lymph node CD4+ T cells (dark agouti background). Proliferation was assayed by incorporation of tritiated deoxythymidine after 2–4 days of culture. Results Allogeneic proliferation stimulated by DCs from the healthy HLA–B27/Huβ 2 m–transgenic line 21‐3 and from the healthy Huβ 2 m‐transgenic line 283‐2 was weakly decreased (21–3) or close to normal (283–2) as compared with that observed with control nontransgenic Lewis rat DCs. In contrast, the ability of DCs from (21‐3 × 283‐2)F 1 rats, which develop a dramatic SpA phenotype, to stimulate allogeneic proliferation was markedly defective. When DC‐induced allogeneic proliferation was compared among different transgenic lines and crosses with distinct levels of susceptibility to SpA‐like disease, stimulatory capacity was inversely correlated with disease susceptibility. Conclusion In HLA–B27/Huβ 2 m–transgenic rats, a defective functional capacity of DCs correlates with susceptibility to SpA. Since it was previously demonstrated that defective DC function is not a consequence of disease, it could well be a principal factor in the spontaneous development of SpA in these lines.