A bias in the α β t cell receptor variable region gene usage in takayasu's arteritis

Abstract

Takayasu's arteritis (TA) is a chronic large vessel vasculitis with a predilection for the aortic arch and its branches. T lymphocytes may be important in the pathogenesis, as they have been found to infiltrate the vascular lesions. To elucidate further the role of T cells in the disease, we studied circulating CD4⁺ and CD8⁺ T cells, expression of the activation marker (HLA-DR), marker for naive (CD45RA) and primed (CD45RO) cells and the different variable α/ β (AV/BV) gene segments on them. The TCR AV/BV repertoire was studied using a panel of 15 T cell receptor (TCR) V-specific MoAbs by flow cytometry in 18 patients and 23 age- and sex-matched controls. Patients had a higher percentage of AV12S1 (P < 0.05), BV6S7 (P < 0.05) and BV9 (P < 0.001)-bearing CD4⁺ cells. Patients also had a higher frequency of expansions, i.e. of T cell populations with an abnormally high TCR AV/BV gene usage. In patients' CD4+ subset of cells, there were 22 expansions out of 231 analyses (9.5%), whereas in controls, four were expanded out of 310 analyses (1%) (P < 0.001). For CD8⁺ cells, the frequency of expansions was 32 in 231 analyses (14%) in patients and nine out of 304 analyses in controls (3%) (P < 0.01). In addition, there was a correlation between CD4+ expansions and disease activity; nine out of 10 patients with active disease in comparison with two out of eight patients with inactive disease (P < 0.01) had an expansion. Some of the expanded populations in patients were phenotypically characterized and observed to be HLA-DR^<, CD28^<, CD45RA^< and CD45RO⁺, with a greater proportion being CD45RO⁺. Patients had a higher percentage of expression of HLA-DR on both CD4⁺ and CD8+ T cells (P < 0.01). The percentages of naive and primed CD4⁺ and CD8⁺ T cells, γ δ+ T cells and natural killer cells were comparable to those in the control group.