CD8αβ T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats

Ekkehard May, Martha L. Dorris, Nimman Satumtira, Imran Iqbal, Muhammad I. Rehman, Ellis Lightfoot, Joel D. Taurog

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

The class I MHC allele HLA-B27 is highly associated with the human spondyloarthropathies, but the basis for this association remains poorly understood. Transgenic rats with high expression of HLA-B27 develop a multisystem inflammatory disease that includes arthritis and colitis. To investigate whether CD8αβ T cells are needed in this disease, we depleted these cells in B27 transgenic rats before the onset of disease by adult thymectomy plus short-term anti-CD8α mAb treatment. This treatment induced profound, sustained depletion of CD8αβ T cells, but failed to suppress either colitis or arthritis. To address the role of CD8α+β- cells, we studied four additional groups of B27 transgenic rats treated with: 1) continuous anti-CD8α mAb, 2) continuous isotype-matched control mAb, 3) the thymectomy/pulse anti-CD8α regimen, or 4) no treatment. Arthritis occurred in ∼40% of each group, but was most significantly reduced in severity in the anti-CD8a-treated group. In addition to CD8αβ T cells, two sizeable CD8α+β- non-T populations were also reduced by the anti-CD8α treatment: 1) NK cells, and 2) a CD4+CD8+CD11b/c+ CD161a+CD172a+ monocyte population that became expanded in diseased B27 transgenic rats. These data indicate that HLA-B27-retricted CD8+ T cells are unlikely to serve as effector cells in the transgenic rat model of HLA-B27-associated disease, in opposition to a commonly invoked hypothesis concerning the role of B27 in the spondyloarthropathies. The data also suggest that one or more populations of CD8α+β- non-T cells may play a role in the arthritis that occurs in these rats.

Original languageEnglish (US)
Pages (from-to)1099-1105
Number of pages7
JournalJournal of Immunology
Volume170
Issue number2
DOIs
StatePublished - Jan 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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