Article Text

AB0052 Polymyalgia rheumatica is characterized by pro-inflammatory, senescent CD8+ T cells
  1. K. van der Geest1,
  2. W. Abdulahad1,
  3. M. Huitema1,
  4. B. Kroesen2,
  5. A. Rutgers1,
  6. E. Brouwer1,
  7. A. Boots1
  1. 1Department of Rheumatology and Clinical Immunology
  2. 2Department of Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands


Background Polymyalgia rheumatica (PMR) is a frequent, inflammatory rheumatic disease affecting elderly people. Previous studies suggest that T cell mediated immune responses contribute to PMR. However, little is known about CD4+ and CD8+ T cell subsets and their function in PMR. Furthermore, it remains to be elucidated if immune ageing contributes to the development of this ageing-related disease. We hypothesized that senescent T cells can functionally contribute to PMR pathogenesis. Therefore, we studied frequencies of circulating T cell subsets in defined stages of differentiation and assessed functional characteristics of senescent (CD28null) T cells in PMR patients.

Objectives The aim of the study is to explore the frequencies and function of distinct T cell subsets in PMR.

Methods Peripheral blood was obtained from eight newly-diagnosed, untreated PMR patients. Thirty-nine healthy age- matched elderly controls were recruited from the Groningen Longevity Cohort. Flow cytometric analysis of CD45RO, CCR7 and CD28 expression was used to enumerate CD4+ and CD8+ T cell differentiation subsets and senescent (CD28null) T cells. Furthermore, naïve and memory regulatory T cells were identified based on CD25 and CD45RA expression. In addition, the prevalence of IFN-gamma, TNF, IL-4 and/or IL-17 producing CD4+ and CD8+ T cells was assessed by intracellular cytokine staining of blood samples from all PMR patients and sixteen elderly controls after 4h in vitro stimulation with PMA/calcium-ionophore in the presence of brefeldin A

Results Compared to healthy controls, PMR patients had decreased percentages of circulating terminally differentiated (CD45RO-CCR7-) CD4+ T cells. However, no differences were observed in the percentages of Th1, Th2, or Th17 cells in PMR patients. In addition, percentages of naïve and memory regulatory T cells were normal in PMR patients. In CD8+ T cells of PMR patients, percentages of naïve (CD45RO-CCR7+) cells were decreased. Interestingly, percentages of CD28null cells were increased within the effector memory (CD45RO+CCR7+) and terminally differentiated CD8+ T cell populations of PMR patients. Moreover, a significantly increased potential to produce IFN-gamma and TNF was observed in CD8+T cells of PMR patients.

Conclusions Our data show premature immune ageing (loss of CD28) of effector memory and terminally differentiated CD8+T cells in PMR patients. This is associated with an enhanced pro-inflammatory potential of CD8+ T cells. In contrast, Th subsets and regulatory T cells are not altered in PMR patients. Together, these findings imply a role for pro-inflammatory, senescent CD8+ T cells in PMR pathogenesis.

Disclosure of Interest None Declared

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