Differential and sequential expression of multiple chemokines during elicitation of allergic contact hypersensitivity

Regulation of chemokine-mediated leukocyte migration within inflammatory ti ssues is a complex event that cannot be mimicked and analyzed in vitro. We therefore investigated the role of macrophage- and T-lymphocyte-specific ch emoattractants involved in the positioning of immune effector cells during the elicitation phase of contact hypersensitivity, a prototype of a T-lymph ocyte-mediated immune reaction. Serial sections of skin biopsies obtained f rom sensitized individuals at distinct time intervals after epicutaneous ap plication of allergens were hybridized with anti-sense probes of a large pa nel of chemokines or immunohistologically labeled with leukocyte-specific a ntibodies. Multifocal expression of monocyte chemoattractant protein-1 (MCP -1) was already detected after 6 hours in basal keratinocytes clearly prece ding the infiltration of monocytes and T cells, Increasing basal expression of MCP-1 and, in addition, of regulated upon activation, normal T-cell exp ressed and secreted (RANTES) after 12 hours was accompanied by dermal expre ssion of MCP-1, macrophage-derived chemoattractant (MDC), and RANTES and pa ralleled by infiltration of mononuclear cells into dermis and epidermis. Ex pression of the T-lymphocyte-specific chemokines IP-10 and MIG in epidermis and dermis and of MDC, pulmonary and activation-regulated chemokine (PARC) , and thymus and activation-regulated chemokine (TARC) exclusively in the d ermis started after 12 hours reaching maximum levels at 72 hours and was as sociated with infiltration of T cells into the epidermal compartment, Our d ata provide evidence that migrating effector cells encounter multiple chemo attractant signals in a complex spatial and temporal pattern, In particular , keratinocytes contribute to the vigorous immigration by sequential expres sion of MCP-1, RANTES, and interferon-inducible protein-10 (IP-10) monokine induced by gamma interferon (MIG), indicating that chemokine-mediated noni mmunological mechanisms precede and corroborate antigen-specific mechanisms during elicitation of contact hypersensitivity.