Experience-driven development: effector/memory-like αE+ Foxp3+ regulatory T cells originate from both naive T cells and naturally occurring naive-like regulatory T …

C Siewert, U Lauer, S Cording, T Bopp… - The Journal of …, 2008 - journals.aai.org
C Siewert, U Lauer, S Cording, T Bopp, E Schmitt, A Hamann, J Huehn
The Journal of Immunology, 2008journals.aai.org
Abstract Naturally occurring Foxp3+ CD25+ CD4+ regulatory T cells (Treg) have initially
been described as anergic cells; however, more recent in vivo studies suggest that Tregs
vigorously proliferate under both homeostatic as well as inflammatory conditions. We have
previously identified a subset of murine CD4+ Tregs, which is characterized by expression of
the integrin α E β 7 and which displays an effector/memory-like phenotype indicative of Ag-
specific expansion and differentiation. In the present study, the α E+ Treg subset was found …
Abstract
Naturally occurring Foxp3+ CD25+ CD4+ regulatory T cells (Treg) have initially been described as anergic cells; however, more recent in vivo studies suggest that Tregs vigorously proliferate under both homeostatic as well as inflammatory conditions. We have previously identified a subset of murine CD4+ Tregs, which is characterized by expression of the integrin α E β 7 and which displays an effector/memory-like phenotype indicative of Ag-specific expansion and differentiation. In the present study, the α E+ Treg subset was found to contain a large fraction of cycling cells under homeostatic conditions in healthy mice. Using an adoptive transfer system of Ag-specific T cells, we could demonstrate that the vast majority of transferred natural, naive-like CD25+ CD4+ Tregs acquired expression of the integrin α E β 7 upon tolerogenic application of Ag via the oral route. In addition, using the same system, Foxp3+ Tregs could be de novo induced from conventional naive CD25− CD4+ T cells, and this conversion was associated with concomitant expression of α E. These findings suggest that Tregs expressing the integrin α E are effector/memory Tregs with a high turnover rate that can develop in the periphery upon Ag contact under tolerogenic conditions, both from thymic-derived CD25+ CD4+ Tregs with a naive-like phenotype as well as from conventional naive T cells.
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