Selective depletion and activation of CD8+ lymphocytes from peripheral blood of patients with polymyalgia rheumatica and giant cell arteritis.

Abstract

SUMMARY A prospective study of 33 patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) was undertaken, firstly, to monitor sequentially peripheral blood CD8+ lymphocyte levels and, secondly, to assess the expression of activation markers on T lymphocyte subsets. The results indicated that there was a significant decrease in absolute numbers and relative percentages of CD8+ T lymphocytes, which returned to normal ranges after approximately 24 months' treatment, and that there was an increased percentage of CD8+ lymphocytes in PMR/GCA which express HLA class II antigens. We undertook a prospective study of patients with PMR/GCA, firstly, to monitor sequentially peripheral blood CD8+ lymphocyte levels and, secondly, to assess the expression of activation markers (HLA class II antigens and interleukin 2 receptor) on T lymphocyte subsets. Our results indicate that there is a profound decrease in absolute numbers of CD8+ T lymphocytes, which return to the normal range after approximately 24 months' treatment and that most CD8+ lymphocytes express class II antigens. Patients and methods PATIENTS AND CONTROLSThirty three patients were investigated. Blood samples were taken sequentially from the onset of disease (and before treatment with corticosteroids) and subsequently every three months up to 24 months. The diagnosis of polymyalgia rheumatica was based on myalgias involving shoulder and pelvic girdle muscle together with morning stiffness and an acute phase reaction (raised C reactive protein and erythrocyte sedimentation rate). Patients with giant cell arteritis were included after a positive temporal artery biopsy. All patients showed rapid and lasting remission of symptoms with corticosteroid treatment

Pathogenesis of polymyalgia rheumatica

“…Beyond the altered distribution of Treg/Th17 cells, Shimojima demonstrated a decrease in activated cytotoxic/suppressor T-cells and increases in circulating Th1 and Tc1 cells in PMR patients (47). A significant decrease in absolute numbers and relative percentages of CD8+ T lymphocytes, inversely correlated with the acute hepatic phase reactants and modified by steroids treatment has been demonstrated in PMR patients (48)(49)(50)(51)(52)(53). The studies performed by Martinez-Taboada and co-workers do not confirm, however, the previous findings that the proportion or number of circulating CD8+ T-cells are reduced in patients with active PMR (53).…”

Pro-inflammatory and anti-inflammatory T cells in giant cell arteritis

“…In general, <5% of tissue-infiltrating cells are CD8 + (31, 32). Reports more than 25 years ago had alerted the community to a selective loss of circulating CD8 T cells, both in percentage and absolute numbers (33–36), with activation markers expressed on remaining CD8 T cells (37). The recent study by Samson et al confirms the polyclonal stimulation of CD8 T cells and points towards higher representation of tissue CD8 T cells in cases of more severe vasculitis (31).…”

Stopping steroids in polymyalgia rheumatica and giant cell arteritis.

“…Dasgupta et al measured serum T cell subsets before and during treatment in polymyalgia rheumatica and giant cell arteritis and found a profound and selective reduction of CD8+ suppressor-cytotoxic cells that persisted for up to one year despite satisfactory control of the disease in terms of symptoms, erythrocyte sedimentation rate, and C reactive protein concentration. 17 After two years of treatment the numbers of CD8 + cells had returned to those found in normal controls. Monitoring CD8+ cells may prove useful in deciding when steroids can be withdrawn.…”