Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment
MetadataShow full item record
© 2015 The Authors. Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently leads to the assumption that Treg presence in prevailing numbers is indicative of immunosuppression. We hypothesized that this assumption may be false. We examined models of three different diseases caused by organ-specific autoimmune responses: primary biliary cirrhosis, atherosclerosis and rheumatoid arthritis (RA). We examined indicators of relative abundance of Treg compared to pro-inflammatory T cells, during peak inflammation. In all cases, the results were compatible with a relative enrichment of Treg at the site of inflammation or its most proximal draining lymph node. Conversely, in healthy mice or mice successfully protected from disease via a Treg-mediated mechanism, the data did not suggest that any Treg accumulation was occurring. This counter-intuitive finding may appear to be at odds with the immunosuppressive nature of Treg. Yet extensive previous studies in RA show that an accumulation of Treg occurs at peak inflammation, albeit without resulting in suppression, as the Treg suppressive function is overcome by the cytokine-rich environment. We suggest that this is a ubiquitous feature of autoimmune inflammation. Treg abundance in patient samples is increasingly used as an indicator of a state of immunosuppression. We conclude that this strategy should be revisited as it may potentially be a source of misinterpretation.
Showing items related by title, author, creator and subject.
Impaired function of regulatory T-cells in patients with chronic obstructive pulmonary disease (COPD)Tan, D.; Fernandez, S.; Price, Patricia; French, M.; Thompson, P.; Moodley, Y. (2014)Anti-inflammatory pathways affecting chronic obstructive pulmonary disease (COPD) are poorly understood. Regulatory T-cells (Tregs) are important negative regulators of T-cell activity and hence were investigated in COPD ...
Low stromal Foxp3+ regulatory T-cell density is associated with complete response to neoadjuvant chemoradiotherapy in rectal cancerMcCoy, M.; Hemmings, C.; Miller, T.; Austin, S.; Bulsara, M.; Zeps, Nikolajs; Nowak, A.; Lake, R.; Platell, C. (2015)© 2015 Cancer Research UK Background:Foxp3+ regulatory T cells (Tregs) play a vital role in preventing autoimmunity, but also suppress antitumour immune responses. Tumour infiltration by Tregs has strong prognostic ...
Increased CTLA-4+ T cells may contribute to impaired T helper type 1 immune responses in patients with chronic obstructive pulmonary diseaseTan, D.; Teo, T.; Setiawan, A.; Ong, N.; Zimmermann, M.; Price, Patricia; Kirkham, L.; Moodley, Y. (2017)Impaired T helper type 1 (Th1) function is implicated in the susceptibility of patients with chronic obstructive pulmonary disease (COPD) to respiratory infections, which are common causes of acute exacerbations of COPD ...