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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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Migration of E-lig+ CD4 memory T cells to TARC, MDC, and CTACK. T lymphocytes from LN draining a cutaneous DTH site were isolated and migrated to TARC, MDC, CTACK, or SLC in a transwell chemotaxis assay (background migration to medium alone is subtracted). Both, E-lig+ and E-lig− wild-type (a) and CCR4−/− (b) CD4 memory T cells migrate equally well to SLC. Chemotaxis to MDC and TARC correlates with E-lig+ expression and is CCR4 dependent as CCR4−/− cells do not respond (a and b). Similarly, E-lig+ but not E-lig− wild-type and CCR4−/− CD4 memory T cells are attracted by CTACK (c and d). The data are mean ± SEM of three to seven experiments.
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fig2: Migration of E-lig+ CD4 memory T cells to TARC, MDC, and CTACK. T lymphocytes from LN draining a cutaneous DTH site were isolated and migrated to TARC, MDC, CTACK, or SLC in a transwell chemotaxis assay (background migration to medium alone is subtracted). Both, E-lig+ and E-lig− wild-type (a) and CCR4−/− (b) CD4 memory T cells migrate equally well to SLC. Chemotaxis to MDC and TARC correlates with E-lig+ expression and is CCR4 dependent as CCR4−/− cells do not respond (a and b). Similarly, E-lig+ but not E-lig− wild-type and CCR4−/− CD4 memory T cells are attracted by CTACK (c and d). The data are mean ± SEM of three to seven experiments.

Mentions: In transwell chemotaxis assays, the E-lig+ subset of T cells derived from draining LN migrates efficiently to CCR4 ligands TARC and MDC. Migration is selective, in that the E-lig-memory phenotype T cells (and naive T cells) respond relatively poorly to the CCR4 ligands (Fig. 2 a), though they migrate well to the CCR7 ligand SLC (Fig. 2 a). Migration to TARC and MDC is CCR4 dependent, as T cells from CCR4-deficient mice do not respond to these CCR4 ligands, but retain their responsiveness to SLC (Fig. 2 b). In addition, both wild-type and CCR4-deficient E-lig+ but not E-lig- CD4 memory T cells migrate to CTACK (Fig. 2, c and d). Thus CTACK, as well as TARC and MDC, attract E-lig+ memory T cells in mouse, as in man.


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)

Migration of E-lig+ CD4 memory T cells to TARC, MDC, and CTACK. T lymphocytes from LN draining a cutaneous DTH site were isolated and migrated to TARC, MDC, CTACK, or SLC in a transwell chemotaxis assay (background migration to medium alone is subtracted). Both, E-lig+ and E-lig− wild-type (a) and CCR4−/− (b) CD4 memory T cells migrate equally well to SLC. Chemotaxis to MDC and TARC correlates with E-lig+ expression and is CCR4 dependent as CCR4−/− cells do not respond (a and b). Similarly, E-lig+ but not E-lig− wild-type and CCR4−/− CD4 memory T cells are attracted by CTACK (c and d). The data are mean ± SEM of three to seven experiments.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Migration of E-lig+ CD4 memory T cells to TARC, MDC, and CTACK. T lymphocytes from LN draining a cutaneous DTH site were isolated and migrated to TARC, MDC, CTACK, or SLC in a transwell chemotaxis assay (background migration to medium alone is subtracted). Both, E-lig+ and E-lig− wild-type (a) and CCR4−/− (b) CD4 memory T cells migrate equally well to SLC. Chemotaxis to MDC and TARC correlates with E-lig+ expression and is CCR4 dependent as CCR4−/− cells do not respond (a and b). Similarly, E-lig+ but not E-lig− wild-type and CCR4−/− CD4 memory T cells are attracted by CTACK (c and d). The data are mean ± SEM of three to seven experiments.
Mentions: In transwell chemotaxis assays, the E-lig+ subset of T cells derived from draining LN migrates efficiently to CCR4 ligands TARC and MDC. Migration is selective, in that the E-lig-memory phenotype T cells (and naive T cells) respond relatively poorly to the CCR4 ligands (Fig. 2 a), though they migrate well to the CCR7 ligand SLC (Fig. 2 a). Migration to TARC and MDC is CCR4 dependent, as T cells from CCR4-deficient mice do not respond to these CCR4 ligands, but retain their responsiveness to SLC (Fig. 2 b). In addition, both wild-type and CCR4-deficient E-lig+ but not E-lig- CD4 memory T cells migrate to CTACK (Fig. 2, c and d). Thus CTACK, as well as TARC and MDC, attract E-lig+ memory T cells in mouse, as in man.

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