The way to the skin

Memory CD4+ T cells express characteristic adhesion molecules and chemokine receptors that dictate their recirculation to the tissue in which they first encountered antigen. On page 1045, Baekkevold and colleagues show that T cells may compete for access to the skin and only gain entry if they express the CC-chemokine receptor-4 (CCR4). Previous studies showed that skin-homing and gut-homing CD4+ T cells express distinct chemokine receptors—CCR4 for skin-homing cells and CCR9 for gut-homing cells—and this was mirrored by the expression of the corresponding chemokine ligand in local blood vessels. The authors thus proposed that expression of CCR4 was required for T cells to access the skin (and CCR9 for the gut) but were perplexed by the phenotype of CCR4-deficient mice, which had normal numbers of skin-homing T cells. Another skin-specific chemokine receptor may have compensated for the absence of CCR4. To test this, Baekkevold et al. staged a competition between wild type and CCR4-deficient bone marrow cells in lymphocyte-deficient mice. They found that CCR4+ cells were highly enriched among lymphocytes that trafficked to the skin, particularly during skin inflammation. This suggested that CCR4, although not essential, facilitated the generation of the skin-homing memory T cell population. Recent studies have shown that tissue-specific dendritic cells (DC) impart CD8+ T cells with specific homing instructions and the authors suspect that a DC-derived signal may trigger CCR4 expression and similarly instruct CD4+ T cells.