A bias in the alphabeta T cell receptor variable region gene usage in Takayasu's arteritis.
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 alpha/beta (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, gammadelta+ T cells and natural killer cells were comparable to those in the control group.
Nityanand
S
S
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Giscombe
R
R
Srivastava
S
S
Hjelmström
P
P
Sanjeevi
C B
CB
Sinha
N
N
Grunewald
J
J
Lefvert
A K
AK
D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006683:HLA-DQ Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016131:Lymphocyte Subsets / Q000166:cytology; D008297:Male; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012217:Rheumatoid Factor / Q000097:blood; D013625:Takayasu Arteritis / Q000235:genetics*
D000974:Antibodies, Antinuclear; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012217:Rheumatoid Factor