Article first published online: 28 MAR 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 4, pages 1134–1135, April 2013
How to Cite
Samson, M., Janikashvili, N., Martin, L., Audia, S. and Bonnotte, B. (2013), Reply. Arthritis & Rheumatism, 65: 1134–1135. doi: 10.1002/art.37863
- Issue published online: 28 MAR 2013
- Article first published online: 28 MAR 2013
- Accepted manuscript online: 17 JAN 2013 03:40PM EST
To the Editor:
We thank Dr. Corbera-Bellalta and colleagues for their interesting comments regarding our work on the implication of Th1, Th17, and Treg cells in GCA and polymyalgia rheumatica (PMR). In our study, we assessed Treg cells in peripheral blood and in temporal artery biopsy samples. We demonstrated that circulating Treg cells were functionally not altered but that percentages of the cells were decreased in the blood of patients with GCA and patients with PMR in comparison with healthy controls. In temporal artery biopsy samples from GCA patients, Th1 cells and Th17 cells, identified by interferon-γ and IL-17 staining, respectively, massively infiltrated the entire arterial wall (Figures 1A and B), whereas FoxP3+ cells were detected at a very low level, especially at the adventitia–media junction, where the inflammatory infiltrate was the most prominent (Figures 1C and D).
We do agree with Corbera-Bellata et al that immunohistochemistry is not the most sensitive technique to detect FoxP3+ T cells. However, in our study, the same technique was used for detection of Treg cells, Th1 cells, and Th17 cells. Even if the number of FoxP3+ cells infiltrating the temporal artery may have been underestimated in our study, there is no doubt that there is a strong imbalance between Th1, Th17, and Treg cells. Furthermore, we demonstrated that a 1:2 ratio of Treg cells to effector T cells was required in vitro to observe efficient suppressive activity. Consequently, even if it is true that we did not detect all FoxP3+ cells because of a lack of sensitivity, these results suggest that their number was not sufficient to suppress Th1 and Th17 immune responses in the artery.
In a recent study, Corbera-Bellata and colleagues interestingly detected FoxP3+IL-17+ T cells in the arterial wall of GCA patients, demonstrating the functional plasticity of T cells regulated by cytokines produced in their microenvironment (1). However, human CD4+ T cells expressing FoxP3+ cannot be systematically considered to be suppressive cells. FoxP3 can indeed be induced in naive CD4+ T cells activated in vitro (2). FoxP3+CD4+ T cell subsets are delineated depending on the level of FoxP3 and CD45RA expression: FoxP3lowCD45RA+ and FoxP3highCD45RA− T cells are immunosuppressive cells, but FoxP3lowCD45RA− T cells are cytokine-secreting nonsuppressive T lymphocytes, and ∼16% of them also produce IL-17 (3). This may suggest that the FoxP3+IL-17+ T cells detected by confocal microscopy in GCA temporal artery biopsy samples (1) are not suppressive Treg cells, but rather, that they are IL-17–producing T cells that coexpress FoxP3 (1, 4).
Dr. Bonnotte has received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline, LFB, and Amgen (less than $10,000 each).
- 1Increased IL-17A expression in temporal artery lesions is a predictor of sustained response to glucocorticoid treatment in patients with giant-cell arteritis. Ann Rheum Dis 2013. E-pub ahead of print., , , , , , et al.
- 2Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol 2007; 37: 129–38., , , , .
- 3Tocilizumab for the treatment of large- vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res (Hoboken) 2012; 64: 1720–9., , , , , , et al.
- 4Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 2009; 30: 899–911., , , , , , et al.
Maxime Samson MD*, Nona Janikashvili PhD, Laurent Martin MD, Sylvain Audia MD, PhD, Bernard Bonnotte MD, PhD, * University of Burgundy, and University Hospital of Dijon, Dijon, France, and INSERM UMR1098, Besançon, France, University of Burgundy, Dijon, France, and INSERM, UMR1098, Besançon, France, University of Burgundy, and University Hospital of Dijon, Dijon, France, and INSERM UMR1098, Besançon, France.