Correlation between dendritic cell functional defect and spondylarthritis phenotypes in HLA-B27/human β2-microglobulin-transgenic rat lines

Ingrid Fert, Simon Glatigny, Cécile Poulain, Nimman Satumtira, Martha L. Dorris, Joel D. Taurog, Maxime Breban

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Objective. To examine the functional capacity of dendritic cells (DCs) from a panel of HLA-B27/human β2-microglobulin (Huβ 2m)-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 Huβ2m- 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/Huβ2m-transgenic line 21-3 and from the healthy Huβ2m-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)F1 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/Huβ2m-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.

Original languageEnglish (US)
Pages (from-to)3425-3429
Number of pages5
JournalArthritis and rheumatism
Volume58
Issue number11
DOIs
StatePublished - Nov 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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