Allergic and irritant contact dermatitis (ACD and ICD) are common inflammatory skin conditions that result after exposure of the cutaneous surface to certain environmental agents (contact sensitizers or haptens). Lack of clear understanding of immunopathogenesis of ACD so far has remained the major hindrance in achieving cure or prevention of these disorders. Effort towards prevention of ACD include identification of environmental agents that induce contact hypersensitivity (CH) response as well as individuals that are susceptible for such a response. Although it is known that certain universal contact sensitizing agents are chemically reactive low molecular weight compounds that can derivatize proteins upon contact and become immunogenic, it is not known why some contact sensitizers do not induce CH in all the individuals. Also, currently available means for the identification of contact allergens can not discriminate between allergens and irritants. In vitro assays designed to identify contact sensitizers so far have met with limited success. These assays have relied on the proliferative responses of T cells, which is a predominant characteristic of a CH response besides inflammation. However, T cell proliferation has remained an inconsistent indicator for distinguishing haptens from irritants. Based on the distinct sensitizing properties of haptens as compared to irritants we propose to develop an in vitro assay that may help identify potential contact sensitizers and irritants as well as individuals susceptible to developing ACD or ICD. We have so far successfully demonstrated the possibility of generating hapten-specific sensitized T cells in vitro cultures in which autologous naive T cells are exposed to hapten derivatized cultured PBMC for 5 days. In order to generate sensitized T cells that closely resemble those found in vivo we now plan to compare effector functions of T cells primed in vivo and in vitro. These comparisons will include phenotype of the T cells proliferating in a hapten-specific manner, their cytokine profile and hapten-specific cytotoxicity. Attempts will be made to compare and contrast T cell responses to various haptens and irritants. Thus, this project can help (a) refine an in vitro assay for future application in clinical laboratory for screening various potential haptens and irritants as well as susceptible individuals and (b) provide better understanding of cellular events that lead to allergic versus irritant contact dermatitis.
