Correlation Between Dendritic Cell Functional Defect and Spondylarthritis Phenotypes in HLA-B27/Humanβ2-Microglobulin-Transgenic Rat Lines
Correlation Between Dendritic Cell Functional Defect and Spondylarthritis Phenotypes in HLA-B27/Humanβ2-Microglobulin-Transgenic Rat Lines
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DOI：
10.1002/art.24023
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发表时间：
2008-11-01
影响因子：
--
通讯作者：
Breban, Maxime
中科院分区：
文献类型：
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作者：
Fert, Ingrid;Glatigny, Simon;Breban, Maxime
Objective. To examine the functional capacity of dendritic cells (DCs) from a panel of HLA-B27/human beta(2)-microglobulin (Hu beta(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 Hu beta(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/Hu beta(2)m-transgenic line 21-3 and from the healthy Hu beta(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 X 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/Hu beta(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.
