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Xue-Song Wu, Anke S. Lonsdorf, Sam T. Hwang 

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1 Cutaneous T-Cell Lymphoma: Roles for Chemokines and Chemokine Receptors 
Xue-Song Wu, Anke S. Lonsdorf, Sam T. Hwang  Journal of Investigative Dermatology  Volume 129, Issue 5, Pages (May 2009) DOI: /jid Copyright © 2009 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Roles for chemokines in CTCL pathyphysiology and therapy. Malignant T cells in CTCL have been shown to express a relatively small number of chemokine receptors. Endothelial cells (EC), keratinocytes (KC), and dendritic cells (DC) all produce a variety of chemokines that can regulate the homing (1) of malignant (and normal) T cells via changes in EC adhesion, stimulated chemotaxis toward epidermis, or movement toward activating DC, respectively. DCs produce chemokines that mediate their adhesion to T cells (for example, Pautrier's microabscesses), thus stimulating activation (2) of these T cells. KC- and DC-derived chemokines have the potential to activate prosurvival pathways that diminish the capacity of T cells to undergo apoptosis (3). Therapeutically, chemokine-tagged T cell antigens (4) that are processed by skin DC have the potential to act as vaccines to enhance a host antitumor immunity toward malignant T cells. Chemokine-tagged toxins (5) have the potential to directly induce cell death in malignant T cells bearing appropriate receptors (for example, CCR4). Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2009 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 CCL27 expression in normal human skin. Frozen sections of normal human skin stained (a) with fluorescent (green) monoclonal antibody specific for human CCL27 or (b) with a control isotype mouse IgG. Sections were counterstained with 4′,6-diamidino-2-phenylindole to visualize nuclei. The dashed white lines indicate the approximate location of the epidermal basement membrane. Bar=10μm, which is indicated in the image on the left. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2009 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 CCL17-PE38 chemotoxin kills CCR4-positive T cells isolated from a patient with SS. CD4+ T cells were isolated from the peripheral blood of a patient with SS. (a) >80% of CD4-gated T cells expressed CCR4 as determined by flow cytometry using a CCR4-specific mAb. For comparison, ∼25% of CD4+ T cells in healthy controls express CCR4 (Narducci et al., 2006). (b) CD4+ SS cells from a patient were exposed to PBS or CCL17-PE chemotoxin (7μgml-1, courtesy of Dr Arya Biragyn, National Institute on aging) (Baatar et al., 2007) for 3 days and then assessed for viability using a vital dye stain (arbitrary optical density units). Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2009 The Society for Investigative Dermatology, Inc Terms and Conditions


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