CD8 alpha beta T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats.

Autor: May E; Harold C. Simmons Arthritis Research Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75390, USA., Dorris ML, Satumtira N, Iqbal I, Rehman MI, Lightfoot E, Taurog JD
Jazyk: angličtina
Zdroj: Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Jan 15; Vol. 170 (2), pp. 1099-105.
DOI: 10.4049/jimmunol.170.2.1099
Abstrakt: 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 CD8alphabeta 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-CD8alpha mAb treatment. This treatment induced profound, sustained depletion of CD8alphabeta T cells, but failed to suppress either colitis or arthritis. To address the role of CD8alpha(+)beta(-) cells, we studied four additional groups of B27 transgenic rats treated with: 1) continuous anti-CD8alpha mAb, 2) continuous isotype-matched control mAb, 3) the thymectomy/pulse anti-CD8alpha regimen, or 4) no treatment. Arthritis occurred in approximately 40% of each group, but was most significantly reduced in severity in the anti-CD8alpha-treated group. In addition to CD8alphabeta T cells, two sizeable CD8alpha(+)beta(-) non-T cell populations were also reduced by the anti-CD8alpha 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 CD8alpha(+)beta(-) non-T cells may play a role in the arthritis that occurs in these rats.
Databáze: MEDLINE