Functionally Relevant Treg Cells Are Present in Giant Cell Arteritis Lesions: Comment on the Article by Samson et al

Authors


To the Editor:

We read with great interest the recently published article by Samson et al (1) on the distribution of circulating CD4+ T lymphocyte subsets (Th1, Th17, CD161+ cells, which are common precursors of Th1, Th17, and Treg cells) in a cohort of 34 patients with active giant cell arteritis (GCA) or polymyalgia rheumatica and 31 healthy controls. Among other interesting and relevant findings, the authors observed an increase in circulating Th17 cells and common Th1/Th17 (CD4+CD161+) precursors, and a decrease in the number, but not function, of Treg cells in peripheral blood. The authors also investigated the presence of lymphocyte subsets in temporal artery lesions from 7 patients and concluded that there were no Treg cells (identified as FoxP3+ cells) in the inflammatory infiltrates of patients with GCA.

In a recent study, we found that FoxP3+ cells, although not predominant, are indeed present in GCA lesions (2). Using quantitative real-time reverse transcription–polymerase chain reaction (RT-PCR), we also found significantly increased expression of FoxP3 messenger RNA (mRNA) in the temporal arteries of 38 untreated GCA patients compared to 19 controls, and demonstrated that expression of FoxP3 mRNA was significantly reduced in 19 specimens from glucocorticoid-treated patients with GCA (2). This accords with a previous study demonstrating the presence of a nonpredominant subset of CD25+ cells in GCA lesions and the decrease in the number of those cells after glucocorticoid treatment (3). Moreover, Treg cells present in GCA lesions are functionally relevant; they may express interleukin-17 (IL-17) in patients with active disease, as demonstrated by immunofluorescence and confocal microscopy, and IL-17 expression by FoxP3+ cells decreases with treatment (2). These observations highlight the functional plasticity of CD4+ T cells depending on inflammatory stimuli and cytokine predominance in the microenvironment (4, 5), as well as the relevance of cells expressing FoxP3 in GCA.

The apparently opposite results described by Samson et al (1) may be due to technical issues. Transcription factors such as FoxP3 are usually expressed at low levels, and immunohistochemistry may not be sensitive enough to detect them in a nonpredominant cell subset. More sensitive techniques, such as real-time RT-PCR or immunofluorescence with confocal microscopy, may be needed to detect FoxP3-expressing cells in GCA-affected arteries. Furthermore, more samples need to be examined, given the wide variability in the density of inflammatory infiltrates in GCA.

A recent study showed that treatment with low-dose IL-2, which results in an increase in the number of Treg cells, reduces vascular inflammation in cryoglobulinemic vasculitis (5), suggesting that Treg cells may be a target for therapeutic manipulation in inflammatory diseases of blood vessels. Therefore, caution is needed before concluding that a potentially important functional T cell subset or biomarker is absent when using techniques with limited sensitivity and/or studying a small number of samples.

Acknowledgements

Supported by grants from the Ministerio de Economía y Competitividad (SAF 08/04328 and SAF 11/30073).

Marc Corbera-Bellalta PhD*, Ester Planas-Rigol PhD*, Georgina Espígol-Frigolé MD*, Ester Lozano PhD*, Maria C. Cid MD*, * Hospital Clinic University of Barcelona, and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.

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