Spondylarthritis in HLA-B27/human β2-microglobulin- transgenic rats is not prevented by lack of CD8

Joel D. Taurog, Martha L. Dorris, Nimman Satumtira, Tri M. Tran, Rohit Sharma, Ralf Dressel, Jens Van Den Brandt, Holger M. Reichardt

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


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 β2-microglobulin (Huβ2m)-transgenic rats. Methods. A missense mutation in the CD8a gene that causes a loss of CD8α 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/Huβ2m- 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/Huβ2m-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. Conclusion. All of the previously described disease manifestations in HLA-B27/Huβ2m- 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.

Original languageEnglish (US)
Pages (from-to)1977-1984
Number of pages8
JournalArthritis and rheumatism
Issue number7
StatePublished - Jul 2009

ASJC Scopus subject areas

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


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