RGD Reference Report - Genetic regulation of T regulatory, CD4, and CD8 cell numbers by the arthritis severity loci Cia5a, Cia5d, and the MHC/Cia1 in the rat. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Genetic regulation of T regulatory, CD4, and CD8 cell numbers by the arthritis severity loci Cia5a, Cia5d, and the MHC/Cia1 in the rat.

Authors: Brenner, M  Laragione, T  Yarlett, NC  Gulko, PS 
Citation: Brenner M, etal., Mol Med. 2007 May-Jun;13(5-6):277-87.
RGD ID: 1642451
Pubmed: PMID:17673937   (View Abstract at PubMed)
PMCID: PMC1936230   (View Article at PubMed Central)
DOI: DOI:10.2119/2007–00003.Brenner   (Journal Full-text)

T cells have a central role in the pathogenesis of autoimmune arthritis, and several abnormalities in T cell homeostasis have been described in rheumatoid arthritis (RA). We hypothesized that T cell phenotypes, including frequencies of different subsets of T regulatory (Treg) cells and in vitro functional responses could be genetically determined. Furthermore, we considered that the genetic contribution would be accounted for by one of the arthritis regulatory quantitative trait loci (QTL), thus providing novel clues to gene mode of action. T cells were isolated from thymus, peripheral blood, and spleen from DA (arthritis-susceptible) and ACI and F344 (arthritis-resistant) strains and from F344.DA(Cia1), DA.F344(Cia5a), and DA.F344(Cia5d) rats congenic for arthritis QTL. T cell subpopulations differed significantly between DA, F344, and ACI. DA rats had an increased frequency of CD4(+) cells, and a reduction in CD8(+) and CD4(+)CD45RC(|o) Treg cells, compared with F344. The differences in CD4/CD8 and CD4(+)CD45RC(|o) Treg cells were accounted for by Cia5a. DA rats also had a reduced frequency of CD8(+)CD45RC(|o) CD25(+) Treg cells compared with F344, and that difference was explained by Cia5d. DA rats also had a significantly lower frequency of CD4(+)CD25(+) and CD8(+)CD25(+) thymocytes, and of peripheral blood CD8(+)CD45RC(|o) Treg cells, compared with F344 rats, and that difference was accounted for by the MHC. This is the first identification of arthritis severity QTL regulating numbers of CD4(+)CD45RC(|o) (Cia5a) and CD8(+)CD45RC(|o) CD25(+) (Cia5d) Treg cells. The MHC effect on CD8(+) Treg cells and CD25(+) thymocytes raises a novel potential explanation for its association with arthritis.



Objects referenced in this article
QTL Cia28 Collagen induced arthritis QTL 28 Rattus norvegicus
QTL Cia5 Collagen induced arthritis QTL 5 Rattus norvegicus
Strain DA.F344-(D10Mit9-D10Rat24)/Nsi null Rattus norvegicus
Strain DA.F344-(D10Rat204-D10Arb22)/Arb null Rattus norvegicus
Strain F344.DA-(D20Arb2-D20Arb8)/Arb null Rattus norvegicus

Additional Information