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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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Related in: MedlinePlus

CD25 single positive cells display a stronger migration into lymph nodes, but αE single positive cells can efficiently enter inflamed sites. (A) Radioactively labeled T cell subsets were injected i.v. into naive Balb/c mice followed by the determination of radioactivity in the indicated organs after 24 h using a γ-counter. Percentage of total recovered radioactivity is shown (n = 4; mean ± SD; one representative out of two independent experiments). (B) Radioactively labeled T cell subsets were injected i.v. in Balb/c mice that had been sensitized and challenged with DNFB. Recovered radioactivity from control and inflamed ear pinna was determined after 24 h (n = 6; mean ± SD; *, P < 0.05; **, P < 0.01).
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fig5: CD25 single positive cells display a stronger migration into lymph nodes, but αE single positive cells can efficiently enter inflamed sites. (A) Radioactively labeled T cell subsets were injected i.v. into naive Balb/c mice followed by the determination of radioactivity in the indicated organs after 24 h using a γ-counter. Percentage of total recovered radioactivity is shown (n = 4; mean ± SD; one representative out of two independent experiments). (B) Radioactively labeled T cell subsets were injected i.v. in Balb/c mice that had been sensitized and challenged with DNFB. Recovered radioactivity from control and inflamed ear pinna was determined after 24 h (n = 6; mean ± SD; *, P < 0.05; **, P < 0.01).

Mentions: First, we investigated the migration behavior of αE− CD25+, αE+CD25+, and αE+CD25−CD4+ Treg subsets, as well as αE−CD25− CD4+ T cells as a control population, in untreated mice (Fig. 5 A). CD25 single positive cells showed a higher migration rate into peripheral and mesenteric lymph nodes compared with αE-expressing Tregs. In contrast, both αE-expressing subsets showed a significantly higher migration rate into the liver. A similar pattern was already detectable at 3 h after injection (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 display a stronger migration into lymph nodes, but αE single positive cells can efficiently enter inflamed sites. (A) Radioactively labeled T cell subsets were injected i.v. into naive Balb/c mice followed by the determination of radioactivity in the indicated organs after 24 h using a γ-counter. Percentage of total recovered radioactivity is shown (n = 4; mean ± SD; one representative out of two independent experiments). (B) Radioactively labeled T cell subsets were injected i.v. in Balb/c mice that had been sensitized and challenged with DNFB. Recovered radioactivity from control and inflamed ear pinna was determined after 24 h (n = 6; mean ± SD; *, P < 0.05; **, P < 0.01).
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Related In: Results  -  Collection

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

fig5: CD25 single positive cells display a stronger migration into lymph nodes, but αE single positive cells can efficiently enter inflamed sites. (A) Radioactively labeled T cell subsets were injected i.v. into naive Balb/c mice followed by the determination of radioactivity in the indicated organs after 24 h using a γ-counter. Percentage of total recovered radioactivity is shown (n = 4; mean ± SD; one representative out of two independent experiments). (B) Radioactively labeled T cell subsets were injected i.v. in Balb/c mice that had been sensitized and challenged with DNFB. Recovered radioactivity from control and inflamed ear pinna was determined after 24 h (n = 6; mean ± SD; *, P < 0.05; **, P < 0.01).
Mentions: First, we investigated the migration behavior of αE− CD25+, αE+CD25+, and αE+CD25−CD4+ Treg subsets, as well as αE−CD25− CD4+ T cells as a control population, in untreated mice (Fig. 5 A). CD25 single positive cells showed a higher migration rate into peripheral and mesenteric lymph nodes compared with αE-expressing Tregs. In contrast, both αE-expressing subsets showed a significantly higher migration rate into the liver. A similar pattern was already detectable at 3 h after injection (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