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. DC produce chemokines that mediate their adhesion to T cells (e.g., 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 anti-tumor immunity toward malignant T cells. Chemokine-tagged toxins (5) have the potential to directly induce cell death in malignant T cells bearing appropriate receptors (e.g., CCR4).

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 monoclonal antibody. 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 (7 ug/ml, courtesy of Dr. Arya Biragyn, National Aging Institute)(Baatar et al., 2007) for three days and then assessed for viability using a vital dye stain (arbitrary optical density units).

Frozen sections of normal human skin with stained with fluorescent (green) monoclonal antibody specific for human CCL27 (A) or with a control isotype mouse IgG (B). Sections were counterstained with DAPI to visualize nuclei. The dashed white lines indicate the approximate location of the epidermal basement membrane.