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. Overstimulated and ineffective