Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment

Stefano Garetto, Anna Elisa Trovato, Ana Lleo, Federica Sala, Elisa Martini, Alexander G. Betz, Giuseppe D. Norata, Pietro Invernizzi, Marinos Kallikourdis

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1025-1029
Number of pages5
JournalImmunobiology
Volume220
Issue number8
DOIs
StatePublished - Aug 1 2015

    Fingerprint

Keywords

  • Atherosclerosis
  • Autoimmunity
  • Inflammation
  • Primary biliary cirrhosis
  • Regulatory T cells
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology

Cite this

Garetto, S., Trovato, A. E., Lleo, A., Sala, F., Martini, E., Betz, A. G., Norata, G. D., Invernizzi, P., & Kallikourdis, M. (2015). Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment. Immunobiology, 220(8), 1025-1029. https://doi.org/10.1016/j.imbio.2015.02.006