Developmental Stage, Phenotype, and Migration Distinguish Naive- and Effector/Memory-like CD4+ Regulatory T Cells

By J. Huehn, K. Siegmund, J. Lehmann, C. Siewert, U. Haubold, M. Feuerer, G. Debes, J. Lauber, O. Frey, G. Przybylski and 7 more. Journal of Experimental Medicine, 2004

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Regulatory T cells (Tregs) fulfill a central role in immune regulation. We reported previously that the integrin αEβ7 discriminates distinct subsets of murine CD4+ regulatory T cells. Use of this marker has now helped to unravel a fundamental dichotomy among regulatory T cells. αE −CD25+ cells expressed L-selectin and CCR7, enabling recirculation through lymphoid tissues. In contrast, αE-positive subsets (CD25+ and CD25−) displayed an effector/memory phenotype expressing high levels of E/P-selectin–binding ligands, multiple adhesion molecules as well as receptors for inflammatory chemokines, allowing efficient migration into inflamed sites. Accordingly, αE-expressing cells were found to be the most potent suppressors of inflammatory processes in disease models such as antigen-induced arthritis.

Subfields: Immunology

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Citations in the corpus

Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment (2019, background): “For their suppressive function, it is crucial that Tregs are able to migrate to the site of inflammation and thus Tregs express high levels of cell adhesion molecules including ICAM-1, L-selectin, P-selectin, and VLA-4 (168).”
Orchestrating the orchestrators: chemokines in control of T cell traffic (2008, background): “Whereas α E − CD25 + T reg cells have abundant expression of CD62L and CCR7 and circulate through lymphoid tissues, α E + CD25 + T reg cells express inflammatory chemokine receptors and several adhesion molecules that allow their migration into nonlymphoid tissue”
CCR7 and its ligands: balancing immunity and tolerance (2008, background): “Natural T Reg cells have been subdivided into two different subpopulations based on their surface expression of CD103: 'naive-like' T Reg cells are CD103 − and 'effector-like' T Reg cells are CD103 + (Ref”
Epigenetic Control of the foxp3 Locus in Regulatory T Cells (2007, methodology): “Cytometric analysis was performed as previously described [”
Regulatory T cells exhibit distinct features in human breast cancer (2016, neutral): “Treg cell expression of homing receptors defines distinct populations that can direct migration to a range of tissues or sites of inflammation (Huehn et al., 2004).”
Phenotypic and functional specialization of FOXP3+ regulatory T cells (2011, background): “However, on entering the periphery, a subset of T Reg cells rapidly acquires phenotypical features of effector or memory T cells, becoming CD44 hi and upregulating expression of homing receptors that allow them to access non-lymphoid site”
Natural Recovery and Protection from Autoimmune Encephalomyelitis: Contribution of CD4+CD25+ Regulatory Cells within the Central Nervous System1 (2005, background): “Expression of the integrin CD103 ( E 7) has recently been shown to correlate with a more potent subpopulation of CD4 CD25 regulatory cells (19, 20) that preferentially migrates to sites of inflammation (19).”
Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. (2007, background): “A distinct gene-expression signature characterizes Foxp3+ Treg cells (Fontenot et al., 2005; Huehn et al., 2004; Herman et al., 2004).”
Intestinal bacterial colonization induces mutualistic regulatory T cell responses. (2011, background): “…cell population showed a high proportion of activated integrin aE (CD103)-expressing effector Treg cells (Figure 1B), which are known to be particularly potent in inhibiting immune responses (Huehn et al., 2004; Lehmann et al., 2002; Siewert et al., 2008; Stephens et al., 2007; Zhao et al., 2008).”
T-bet controls regulatory T cell homeostasis and function during type-1 inflammation (2009, background): “T reg cells can be categorized into several subsets based on their differential expression of surface-homing receptors and can be readily identified in both lymphoid and nonlymphoid tissue”