General autoimmunity

Oral

cd25lowfoxp3+ T Cells Are Derived from a Regulatory T Cell Lineage and Are Circulating Markers of Active Autoimmunity

Thursday, June 15
5:45 PM - 7:00 PM

Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process.  Although the disease mechanisms leading to the break of tolerance are largely unknown, alterations in FOXP3+ regulatory CD4+ T cells (Tregs) have been implicated in the pathogenesis of several autoimmune diseases, including type 1 diabetes (T1D) and systemic lupus erythematosus (SLE).  Here we found that the frequency of FOXP3+ cells within CD127lowCD25low CD4+ T cells (here defined as CD25lowFOXP3+ T cells) is increased compared to healthy donors in several autoimmune diseases of varying disease severity, including SLE, severe immunodeficiency patients with active autoimmunity and T1D patients.  In this study, we show that CD25lowFOXP3+ T cells share phenotypic features resembling conventional CD127lowCD25highFOXP3+ Tregs, including demethylation of the Treg-specific epigenetic control region in FOXP3 and lack of IL-2 production.  As compared to conventional Tregs, more CD25lowFOXP3+ T cells are in cell cycle (29.9% vs 22.0% Ki-67+; P = 2.7 x 10-7) and express the late-stage inhibitory receptor PD-1 (65.1% vs 38.3%; P = 1.7 x 10-17), while downregulating the expression of the early-stage inhibitory receptor CTLA-4, as well as other classical Treg markers, such as FOXP3, HELIOS and TIGIT.  These findings suggest that CD25lowFOXP3+ T cells represent a late stage of Treg differentiation in vivo, and are a peripheral biomarker of recent Treg expansion in response to an autoimmune reaction in tissues.

Ricardo C. Ferreira

Post Doctoral Fellow
University of Oxford

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    Daniel Rainbow

    University of Oxford

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      Tony Cutler

      University of Oxford

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        Tim Vyse

        King's College London

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          Helen Baxendale

          Addenbrooke's Hospital

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            Anita Chandra

            Addenbrooke's Hospital

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              John Todd

              University of Oxford

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                Linda Wicker

                University of Oxford

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                  Marcin Pekalski

                  University of Oxford

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