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

Abstract

Backgroundand objectives Polymyalgia rheumatica (PMR) is a frequent, inflammatory rheumatic disease affecting older 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 whether immune ageing contributes to the development of this age-related disease. The authors hypothesised that senescent T cells can functionally contribute to PMR pathogenesis. Therefore, the authors studied frequencies of circulating T cell subsets in defined stages of differentiation and assessed characteristics of senescent (CD28 null) T cells in PMR patients.

Materials and methods Peripheral blood was obtained from eight newly-diagnosed, untreated PMR patients. Thirty-nine healthy age- matched older 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, full blood of all PMR patients and eleven older controls was stimulated with PMA/calcium-ionophore in the presence of brefeldin A during 4 h. This was followed by intracellular staining for IFNγ, TNF, IL-4 and IL-17.

Results Compared to healthy controls, PMR patients had decreased percentages of circulating terminally differentiated (CD45RO-CCR7-) CD4+ T cells. However, the authors did not observe altered 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 a strong trend towards more TNF production were observed in CD8+T cells of PMR patients.

Conclusions Our data showed premature immune ageing (loss of CD28) of effector memory and terminally differentiated CD8+T cells in PMR-patients. This was associated with an enhanced pro-inflammatory potential of CD8+ T cells. In contrast, the authors observed no clear alterations of Th-subsets and regulatory T cells in PMR patients. Altogether, these findings imply a role for late stage CD8+ T cells in PMR pathogenesis.

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