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CC chemokine receptor (CCR)4 and the CCR10 ligand cutaneous T cell-attracting chemokine (CTACK) in lymphocyte trafficking to inflamed skin.

Reiss Y, Proudfoot AE, Power CA, Campbell JJ, Butcher EC - J. Exp. Med. (2001)

Bottom Line: In 24 h in vivo homing assays, stimulated lymph node T cells from wild-type mice or, surprisingly, from CCR4-deficient donors migrate efficiently to inflamed skin; and an inhibitory anti-CTACK antibody has no effect on wild-type lymphocyte recruitment.However, inhibition with anti-CTACK monoclonal antibody abrogates skin recruitment of CCR4-deficient T cells.We conclude that CTACK and CCR4 can both support homing of T cells to skin, and that either one or the other is required for lymphocyte recruitment in cutaneous delayed type hypersensitivity.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

ABSTRACT
The chemokine thymus and activation-regulated chemokine (TARC; CCL17) is displayed by cutaneous (but not intestinal) venules, and is thought to trigger vascular arrest of circulating skin homing memory T cells, which uniformly express the TARC receptor CC chemokine receptor (CCR)4. Cutaneous T cell-attracting chemokine (CTACK; CCL27), expressed by skin keratinocytes, also attracts cutaneous memory T cells, and is hypothesized to assist in lymphocyte recruitment to skin as well. Here we show that chronic cutaneous inflammation induces CD4 T cells expressing E-selectin binding activity (a marker of skin homing memory cells) in draining lymph node, and that these E-selectin ligand+ T cells migrate efficiently to TARC and to CTACK. In 24 h in vivo homing assays, stimulated lymph node T cells from wild-type mice or, surprisingly, from CCR4-deficient donors migrate efficiently to inflamed skin; and an inhibitory anti-CTACK antibody has no effect on wild-type lymphocyte recruitment. However, inhibition with anti-CTACK monoclonal antibody abrogates skin recruitment of CCR4-deficient T cells. We conclude that CTACK and CCR4 can both support homing of T cells to skin, and that either one or the other is required for lymphocyte recruitment in cutaneous delayed type hypersensitivity.

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Related in: MedlinePlus

CCR4 and CTACK-dependent reduction of ear swelling in a cutaneous DTH reaction. Thy1.1 congenic recipients were treated with anti-CTACK mAb or the isotype control before the adoptive transfer of immunized Thy1.2+ donor LN cells. Recipient or control mouse ears were stimulated by local application of DNFB. Swelling induced by transferred CCR4−/− but not by wild-type immune T cells is blocked with a mAb against CTACK. Background swelling of DNFB treated recipients without donor cells has been subtracted (mean ± SEM of seven experiments).
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fig5: CCR4 and CTACK-dependent reduction of ear swelling in a cutaneous DTH reaction. Thy1.1 congenic recipients were treated with anti-CTACK mAb or the isotype control before the adoptive transfer of immunized Thy1.2+ donor LN cells. Recipient or control mouse ears were stimulated by local application of DNFB. Swelling induced by transferred CCR4−/− but not by wild-type immune T cells is blocked with a mAb against CTACK. Background swelling of DNFB treated recipients without donor cells has been subtracted (mean ± SEM of seven experiments).

Mentions: Adoptive transfer of immunized LN cells confers T cell-dependent enhanced ear swelling, the hallmark of DTH, in response to DNFB challenge (14). To determine if this T cell–dependent swelling requires CCR4 or CTACK, the ability of CCR4-deficient lymphocytes to mediate swelling, and the effect of anti-CTACK mAb on wild-type and CCR4-deficient donor T cell–mediated responses was assessed (Fig. 5). Paralleling the results for T cell homing, neither CCR4 deficiency of transferred LN cells, nor anti-CTACK mAb in the setting of wild-type cell transfer, substantially inhibited swelling. However, anti-CTACK dramatically and consistently inhibited swelling induced by CCR4-deficient cells.


CC chemokine receptor (CCR)4 and the CCR10 ligand cutaneous T cell-attracting chemokine (CTACK) in lymphocyte trafficking to inflamed skin.

Reiss Y, Proudfoot AE, Power CA, Campbell JJ, Butcher EC - J. Exp. Med. (2001)

CCR4 and CTACK-dependent reduction of ear swelling in a cutaneous DTH reaction. Thy1.1 congenic recipients were treated with anti-CTACK mAb or the isotype control before the adoptive transfer of immunized Thy1.2+ donor LN cells. Recipient or control mouse ears were stimulated by local application of DNFB. Swelling induced by transferred CCR4−/− but not by wild-type immune T cells is blocked with a mAb against CTACK. Background swelling of DNFB treated recipients without donor cells has been subtracted (mean ± SEM of seven experiments).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193675&req=5

fig5: CCR4 and CTACK-dependent reduction of ear swelling in a cutaneous DTH reaction. Thy1.1 congenic recipients were treated with anti-CTACK mAb or the isotype control before the adoptive transfer of immunized Thy1.2+ donor LN cells. Recipient or control mouse ears were stimulated by local application of DNFB. Swelling induced by transferred CCR4−/− but not by wild-type immune T cells is blocked with a mAb against CTACK. Background swelling of DNFB treated recipients without donor cells has been subtracted (mean ± SEM of seven experiments).
Mentions: Adoptive transfer of immunized LN cells confers T cell-dependent enhanced ear swelling, the hallmark of DTH, in response to DNFB challenge (14). To determine if this T cell–dependent swelling requires CCR4 or CTACK, the ability of CCR4-deficient lymphocytes to mediate swelling, and the effect of anti-CTACK mAb on wild-type and CCR4-deficient donor T cell–mediated responses was assessed (Fig. 5). Paralleling the results for T cell homing, neither CCR4 deficiency of transferred LN cells, nor anti-CTACK mAb in the setting of wild-type cell transfer, substantially inhibited swelling. However, anti-CTACK dramatically and consistently inhibited swelling induced by CCR4-deficient cells.

Bottom Line: In 24 h in vivo homing assays, stimulated lymph node T cells from wild-type mice or, surprisingly, from CCR4-deficient donors migrate efficiently to inflamed skin; and an inhibitory anti-CTACK antibody has no effect on wild-type lymphocyte recruitment.However, inhibition with anti-CTACK monoclonal antibody abrogates skin recruitment of CCR4-deficient T cells.We conclude that CTACK and CCR4 can both support homing of T cells to skin, and that either one or the other is required for lymphocyte recruitment in cutaneous delayed type hypersensitivity.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

ABSTRACT
The chemokine thymus and activation-regulated chemokine (TARC; CCL17) is displayed by cutaneous (but not intestinal) venules, and is thought to trigger vascular arrest of circulating skin homing memory T cells, which uniformly express the TARC receptor CC chemokine receptor (CCR)4. Cutaneous T cell-attracting chemokine (CTACK; CCL27), expressed by skin keratinocytes, also attracts cutaneous memory T cells, and is hypothesized to assist in lymphocyte recruitment to skin as well. Here we show that chronic cutaneous inflammation induces CD4 T cells expressing E-selectin binding activity (a marker of skin homing memory cells) in draining lymph node, and that these E-selectin ligand+ T cells migrate efficiently to TARC and to CTACK. In 24 h in vivo homing assays, stimulated lymph node T cells from wild-type mice or, surprisingly, from CCR4-deficient donors migrate efficiently to inflamed skin; and an inhibitory anti-CTACK antibody has no effect on wild-type lymphocyte recruitment. However, inhibition with anti-CTACK monoclonal antibody abrogates skin recruitment of CCR4-deficient T cells. We conclude that CTACK and CCR4 can both support homing of T cells to skin, and that either one or the other is required for lymphocyte recruitment in cutaneous delayed type hypersensitivity.

Show MeSH
Related in: MedlinePlus