Cell trafficking in positive and negative patch-test reactions: demonstration of a stereotypic migration pathway

The cellular and molecular events taking place during epidermal antigen exposure in sensitized individuals are principally well understood. Epidermal Langerhans cells (LC) are supposed to take up, process, and express a given foreign substance on their cell surface. The antigen is then recognized by T cells bearing the appropriate T-cell receptor (TCR). Because LC do not bear variable antigen (Ag)-specific binding sites, one could postulate that the epidermal exposure of any substance should activate LC and other cells of the skin immune system. To test this hypothesis, we analyzed immunophenotypically the cellular trafficking events in positive (n = 5) and negative epicutaneous patch-test reactions (n = 10), using a panel of monoclonal antibodies against CD1a, CD11c (Ki-M1, LeuM5), CD68 (Ki-M6), Ki-M8, and CD3 (Leu4). We can demonstrate that irrespective of whether or not an antigen will be responded to by the immune system (i.e., positive or negative test reaction), epidermal antigen exposure causes a decrease of LC density in the epidermis and simultaneously causes an increase of LC in the dermis. Moreover, monocytes and T cells immigrate into the dermis both in positive and negative patch-test reactions. As is to be expected, the degree of this cellular traffic is more pronounced in positive test reactions, which may be due to amplification mechanisms caused by antigen recognition of sensitized T cells. This finding demonstrates that human skin contains cell migration programs that ensure that any foreign substance will be accessible to the skin immune and phagocytic system.