CHEMOKINE EXPRESSION IN TRINITROCHLORABENZENE-MEDIATED CONTACT HYPERSENSITIVITY

The expression of the murine IP-10 and MCP-1 genes has been examined i n the skin of mice during contact hypersensitivity reactions to the ha pten trinitrochlorobenezene (TNCB). In both naive and passively sensit ized animals, challenge with TNCB resulted in elevated expression of b oth genes as early as 4 h as detected by Northern hybridization analys is. Twenty-four hours after challenge, expression was markedly reduced in naive animals but remained elevated in sensitized animals. This pr olonged expression of chemokine gene products correlates with the tiss ue swelling response generally used as a measure of delayed-type hyper sensitivity (DTH) in this model and suggests that the continued expres sion of these genes results from the stimulation of hapten-specific T helper cells. Examination of cell type expression patterns by in situ hybridization using H-3-radiolabeled riboprobes confirmed the results of Northern hybridization experiments. Both genes were expressed predo minantly in cells exhibiting the morphology of connective tissue fibro blasts, although the distribution of cells positive for IP-10 mRNA exp ression differed from that of cells expressing MCP-1 mRNA. IP-10 expre ssion was localized almost exclusively to a population of connective t issue cells surrounding the fur follicle. MCP-1 expression was rarely found associated with fur follicles but instead was distributed throug hout the dermis in cells embedded in the collagenous extracellular mat rix. Surprisingly, neither endothelial cells lining the small vessels located deep within the dermis nor epidermal keratinocytes were positi ve under any of the conditions utilized in the present study. Expressi on of both IP-10 and MCP-1 has been previously reported in a variety o f distinct cell types in vitro. The present results indicate that only a subset of the cell types with such potential are stimulated to expr ess these chemokine genes in vivo during hapten-mediated DTH responses , implying the presence of subtle cell type- and tissue-specific contr ol mechanisms.