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T Cells Are Not Essential to the Pathogenesis of Arthritis or Colitis in HLA-B27 Transgenic Rats1
Harold C. Simmons Arthritis Research Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390
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 CD8
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-CD8
mAb treatment. This treatment induced profound, sustained depletion of
CD8 T cells, but failed to suppress either colitis or arthritis.
To address the role of CD8+- cells, we
studied four additional groups of B27 transgenic rats treated with: 1)
continuous anti-CD8 mAb, 2) continuous isotype-matched control
mAb, 3) the thymectomy/pulse anti-CD8 regimen, or 4) no
treatment. Arthritis occurred in 
40% of each group, but was most
significantly reduced in severity in the anti-CD8-treated group.
In addition to CD8 T cells, two sizeable
CD8+- non-T cell populations were also
reduced by the anti-CD8 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 CD8+- non-T cells may
play a role in the arthritis that occurs in these
rats.
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