Correlation between dendritic cell functional defect and spondylarthritis phenotypes in HLA-B27/HUMAN beta2-microglobulin-transgenic rat lines.
OBJECTIVE
To examine the functional capacity of dendritic cells (DCs) from a panel of HLA-B27/human beta2-microglobulin (Hubeta2m)-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 Hubeta2m-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/Hubeta2m-transgenic line 21-3 and from the healthy Hubeta2m-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.


CONCLUSIONS
In HLA-B27/Hubeta2m-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.
Fert
Ingrid
I
Institut Cochin, INSERM U567, CNRS UMR8104, IFR 116, Université Paris-Descartes, Paris, France.
Glatigny
Simon
S
Poulain
Cécile
C
Satumtira
Nimman
N
Dorris
Martha L
ML
Taurog
Joel D
JD
Breban
Maxime
M
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D004198:Disease Susceptibility; D015796:HLA-B27 Antigen / Q000235:genetics*; D008297:Male; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D025241:Spondylarthritis / Q000235:genetics*; D001613:beta 2-Microglobulin / Q000235:genetics*
D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin