CHEMOKINE EXPRESSION IN TRINITROCHLORABENZENE-MEDIATED CONTACT HYPERSENSITIVITY

The expression of the murine IP-10 and MCP-1 genes has been examined in the skin of mice during contact hypersensitivity reactions to the hapten trinitrochlorobenezene (TNCB). In both naive and passively sensitized animals, challenge with TNCB resulted in elevated expression of both genes as early as 4 h as detected by Northern hybridization analysis. Twenty-four hours after challenge, expression was markedly reduced in naive animals but remained elevated in sensitized animals. This prolonged expression of chemokine gene products correlates with the tissue swelling response generally used as a measure of delayed-type hypersensitivity (DTH) in this model and suggests that the continued expression 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 predominantly in cells exhibiting the morphology of connective tissue fibroblasts, although the distribution of cells positive for IP-10 mRNA expression differed from that of cells expressing MCP-1 mRNA. IP-10 expression was localized almost exclusively to a population of connective tissue cells surrounding the fur follicle. MCP-1 expression was rarely found associated with fur follicles but instead was distributed throughout the dermis in cells embedded in the collagenous extracellular matrix. Surprisingly, neither endothelial cells lining the small vessels located deep within the dermis nor epidermal keratinocytes were positive under any of the conditions utilized in the present study. Expression of both IP-10 and MCP-1 has been previously reported in a variety of distinct cell types in vitro. The present results indicate that only a subset of the cell types with such potential are stimulated to express these chemokine genes in vivo during hapten-mediated DTH responses, implying the presence of subtle cell type- and tissue-specific control mechanisms.