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Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells.

Huehn J, Siegmund K, Lehmann JC, Siewert C, Haubold U, Feuerer M, Debes GF, Lauber J, Frey O, Przybylski GK, Niesner U, de la Rosa M, Schmidt CA, Bräuer R, Buer J, Scheffold A, Hamann A - J. Exp. Med. (2004)

Bottom Line: We reported previously that the integrin alphaEbeta7 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. alphaE-CD25+ cells expressed L-selectin and CCR7, enabling recirculation through lymphoid tissues.Accordingly, alphaE -expressing cells were found to be the most potent suppressors of inflammatory processes in disease models such as antigen-induced arthritis.

View Article: PubMed Central - PubMed

Affiliation: Experimentelle Rheumatologie, Medizinische Klinik, Charité, Humboldt-Universitaet, Schumannstr. 21/22, 10117 Berlin, Germany. Huehn@drfz.de

ABSTRACT
Regulatory T cells (Tregs) fulfill a central role in immune regulation. We reported previously that the integrin alphaEbeta7 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. alphaE-CD25+ cells expressed L-selectin and CCR7, enabling recirculation through lymphoid tissues. In contrast, alphaE -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, alphaE -expressing cells were found to be the most potent suppressors of inflammatory processes in disease models such as antigen-induced arthritis.

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CD25 single positive cells represent natural Tregs, whereas αE-expressing subsets are prototypes of adaptive Tregs.
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fig7: CD25 single positive cells represent natural Tregs, whereas αE-expressing subsets are prototypes of adaptive Tregs.

Mentions: A model recently suggested by Bluestone et al. reconciles the functional and developmental heterogeneity among Tregs in proposing the existence of natural and adaptive regulators differing not only in terms of origin but also of specificity and effector mechanisms (11). According to their model, natural, self-antigen–specific Tregs develop during the normal process of T cell maturation in the thymus and survive as a long-lived population in the periphery, poised to sustain self-tolerance. In contrast, adaptive Tregs develop upon T cell activation under particular conditions. Several sets of data in the present work provide evidence that the expression of CD25 and αE can be used to differentiate these subsets in the murine system; their differential developmental stage according to TREC content and effector/memory markers as well as unique migratory phenotypes consistently define them as distinct subsets. Apparently, CD25 single positive and αE-expressing cells can be envisaged as prototypes of natural and adaptive Tregs, respectively, with the adaptive regulators developing either from thymus-derived natural Tregs or from naive cells upon encounter with cognate antigen (Fig. 7). In accordance with this, only CD25 single positive cells were detected in significant frequencies among CD4+CD8− cells in thymus early after birth (unpublished data).


Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells.

Huehn J, Siegmund K, Lehmann JC, Siewert C, Haubold U, Feuerer M, Debes GF, Lauber J, Frey O, Przybylski GK, Niesner U, de la Rosa M, Schmidt CA, Bräuer R, Buer J, Scheffold A, Hamann A - J. Exp. Med. (2004)

CD25 single positive cells represent natural Tregs, whereas αE-expressing subsets are prototypes of adaptive Tregs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211798&req=5

fig7: CD25 single positive cells represent natural Tregs, whereas αE-expressing subsets are prototypes of adaptive Tregs.
Mentions: A model recently suggested by Bluestone et al. reconciles the functional and developmental heterogeneity among Tregs in proposing the existence of natural and adaptive regulators differing not only in terms of origin but also of specificity and effector mechanisms (11). According to their model, natural, self-antigen–specific Tregs develop during the normal process of T cell maturation in the thymus and survive as a long-lived population in the periphery, poised to sustain self-tolerance. In contrast, adaptive Tregs develop upon T cell activation under particular conditions. Several sets of data in the present work provide evidence that the expression of CD25 and αE can be used to differentiate these subsets in the murine system; their differential developmental stage according to TREC content and effector/memory markers as well as unique migratory phenotypes consistently define them as distinct subsets. Apparently, CD25 single positive and αE-expressing cells can be envisaged as prototypes of natural and adaptive Tregs, respectively, with the adaptive regulators developing either from thymus-derived natural Tregs or from naive cells upon encounter with cognate antigen (Fig. 7). In accordance with this, only CD25 single positive cells were detected in significant frequencies among CD4+CD8− cells in thymus early after birth (unpublished data).

Bottom Line: We reported previously that the integrin alphaEbeta7 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. alphaE-CD25+ cells expressed L-selectin and CCR7, enabling recirculation through lymphoid tissues.Accordingly, alphaE -expressing cells were found to be the most potent suppressors of inflammatory processes in disease models such as antigen-induced arthritis.

View Article: PubMed Central - PubMed

Affiliation: Experimentelle Rheumatologie, Medizinische Klinik, Charité, Humboldt-Universitaet, Schumannstr. 21/22, 10117 Berlin, Germany. Huehn@drfz.de

ABSTRACT
Regulatory T cells (Tregs) fulfill a central role in immune regulation. We reported previously that the integrin alphaEbeta7 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. alphaE-CD25+ cells expressed L-selectin and CCR7, enabling recirculation through lymphoid tissues. In contrast, alphaE -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, alphaE -expressing cells were found to be the most potent suppressors of inflammatory processes in disease models such as antigen-induced arthritis.

Show MeSH
Related in: MedlinePlus