Abstract
Objectives: To investigate the phenotype and T cell receptor (TCR) use in peripheral blood T cells in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA).
Methods: Circulating T lymphocyte phenotype and TCR repertoire were studied by flow cytometry using specific monoclonal antibodies in 23 healthy controls and 37 patients with PMR/GCA.
Results: Patients with active PMR/GCA showed an inverse relation between naive and memory CD4+ T cells and unchanged expression of activation surface markers compared with controls. CD4+ TCR BV expansions were seen in 12 (52%) controls and in 8 (22%) patients with active disease (p = 0.03). Within the CD8+ subset, the frequency of expansions was similar between groups. Most T cell expansions remained stable over time. Seventeen of the 23 patients with active PMR/GCA disclosed a simultaneous CD4+ and CD8+ T cell depletion for at least one particular BV family with a clear predominance of BV5S2/S3.
Conclusions: The phenotype of circulating T cells in patients with PMR/GCA is similar to that found in aged healthy subjects, except for the surface markers of naive and memory cells and a striking non-activated phenotype. Specific BV expansions in CD4+ and CD8+ T cells, which remain stable over time, are frequent in aged subjects, including patients with PMR/GCA. TCR BV changes in patients with active disease seem to be also age related, except for the significant decrease in certain BV families in both CD4+ and CD8+ T cell subsets, which may favour the participation of a superantigen stimulation in PMR/GCA.
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Figure 1 .
Frequency of TCR BV expansions in CD4+ and CD8+ in patients with PMR/GCA and healthy age matched controls. Peripheral blood TCR BV use was determined by flow cytometry. TCR BV specific expansion was defined as BV specificities expressed at a frequency greater than the mean + 3SD of a young healthy population or as a value of more than 20%. Patients with active disease showed a lower frequency of CD4+ TCR BV expansions than healthy controls or patients with controlled disease after steroid treatment.
Figure 2 .
Distribution of TCR BV expansions in patients with PMR/GCA and in healthy age matched controls. TCR expansions of one or more BV families were seen in patients and controls in both CD4+ T cell subsets (A) and CD8+ T cell subsets (B).
Figure 3 .
Longitudinal analysis of TCR BV expansions in patients with active PMR/GCA. Before steroid treatment four patients with PMR/GCA carried six expanded populations, four within the CD4+ (black squares) subset and two in the CD8+ (black circles) T cells. After six months of treatment, four of the expanded populations remained stable over time, two increased more than 30% (patient B), and a new expansion appeared (patient D).
Figure 4 .
Microbial superantigen hypothesis for the development of PMR and GCA. Ag, antigen.
Selected References
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