Abstract
Foxp3+ T-regulatory cells (Tregs) normally serve to attenuate immune responses and are key to maintenance of immune homeostasis. Over the past decade, Treg cells have become a major focus of research for many groups, and various functional subsets have been characterized. Recently, the Ikaros family member, Helios, was reported as a marker to discriminate naturally occurring, thymic-derived Tregs from those peripherally induced from naïve CD4+ T cells. We investigated Helios expression in murine and human T cells under resting or activating conditions, using well-characterized molecules of naïve/effector/memory phenotypes, as well as a set of Treg-associated markers. We found that Helios-negative T cells are enriched for naïve T cell phenotypes and vice versa. Moreover, Helios can be induced during T cell activation and proliferation, but regresses in the same cells under resting conditions. We demonstrated comparable findings using human and murine CD4+Foxp3+ Tregs, as well as in CD4+ and CD8+ T cells. Since Helios expression is associated with T cell activation and cellular division, regardless of the cell subset involved, it does not appear suitable as a marker to distinguish natural and induced Treg cells.
Highlights
T-regulatory cells (Tregs) constitute a functionally important subset of lymphocytes capable of fine tuning the immune response against pathogens and environmental stimuli [1]
Defining functional subsets of Treg is even more complicated, though Tregs can be divided into the two broad categories of natural occurring thymus-derived Tregs, and peripherally induced Tregs that can develop from naıve T cells under a variety of conditions [7]
In human CD4+ cells, the highest levels of Helios expression were associated with Foxp3, CD25, CD39, CTLA-4 (CD152) and low levels of CD127, while intermediately positive Helios+ cells included non-Treg cells (Figure 1B)
Summary
T-regulatory cells (Tregs) constitute a functionally important subset of lymphocytes capable of fine tuning the immune response against pathogens and environmental stimuli [1]. Defining functional subsets of Treg is even more complicated, though Tregs can be divided into the two broad categories of natural occurring thymus-derived Tregs (nTreg), and peripherally induced Tregs (iTreg) that can develop from naıve T cells under a variety of conditions [7]. Both subsets share similar molecular signatures, including expression of Foxp, high expression of CD25 [8] and CTLA-4 [9], and low expression of CD127 [10], and share multiple suppressive mechanisms [11]. Being able to determine the origin of a given Treg may be of importance in basic studies of Treg biology, or when monitoring the success of therapeutic interventions aimed at altering Treg production or function
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