title: Spondylarthritis in HLA-B27/human beta2-microglobulin-transgenic rats is not prevented by lack of CD8.
abstract: OBJECTIVE
  HLA-B27 predisposes to spondylarthritis by an unknown mechanism. A logical candidate mechanism is through recognition of B27 by CD8+ T cells. The purpose of this study was to examine the effects of a lack of CD8 on the spondylarthritis that develops in B27/human beta(2)-microglobulin (Hubeta(2)m)-transgenic rats.
  
  
  METHODS
  A missense mutation in the CD8a gene that causes a loss of CD8alpha expression was identified in offspring of a male Sprague-Dawley rat that had been treated with the mutagen N-ethyl-N-nitrosourea. The mutation was crossed into B27/Hubeta(2)m-transgenic lines on the Lewis background. CD8a(-/-) and CD8a(+/-) progeny were compared on a mixed SD-LEW background as well as after at least 10 backcrosses to LEW rats. CD8 function was assessed by generating cytolytic T lymphocytes (CTLs) against allogeneic DA strain antigens.
  
  
  RESULTS
  Homozygous mutant rats showed normal CD8a and CD8b messenger RNA levels but no detectable expression of either protein and an almost complete abrogation of the allogeneic CTL response. Two disease phenotypes previously observed in different B27/Hubeta(2)m-transgenic lines also occurred in the respective CD8a(-/-)-transgenic rat lines. There was no significant difference in disease prevalence or severity between CD8a(-/-) rats and CD8a(+/-) rats.
  
  
  CONCLUSIONS
  All of the previously described disease manifestations in HLA-B27/Hubeta(2)m-transgenic rats arise in the absence of any functional CD8+ T cells. It thus seems unlikely that classic T cell recognition of HLA-B27 is of primary importance in this animal model. The possibility of a secondary role of a CD8-dependent mechanism cannot be entirely excluded.
authors: University of Texas Southwestern Medical Center, Dallas, TX 75390-8884, USA. joel.taurog@utsouthwestern.edu
authors: Joel D
authors: JD
authors: Taurog
authors: Martha L
authors: ML
authors: Dorris
authors: Nimman
authors: N
authors: Satumtira
authors: Tri M
authors: TM
authors: Tran
authors: Rohit
authors: R
authors: Sharma
authors: Ralf
authors: R
authors: Dressel
authors: Jens
authors: J
authors: van den Brandt
authors: Holger M
authors: HM
authors: Reichardt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012720:Severity of Illness Index; D025241:Spondylarthritis / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D001613:beta 2-Microglobulin / Q000235:genetics*
chemical_list: D016827:CD8 Antigens; D015796:HLA-B27 Antigen; D012333:RNA, Messenger; D001613:beta 2-Microglobulin