CONTRIBUTION OF THE CD28 MOLECULE TO ALLERGIC AND IRRITANT-INDUCED SKIN REACTIONS IN CD28 - - MICE/

The CD28 molecule is thought to be essential for the costimulatory sig nals and is required for mitogenic activation of T cells, The aim of t his study was to Evaluate the contribution of CD28 in contact hypersen sitivity using CD28 gene-targeted (CD28-/-) mutant mice, Contact hyper sensitivity to dinitrofluorobenzene and oxazolone was significantly de creased in CD28-/- mice compared with that in normal (C57BL/6) mice, S ignificant increases in IL-2 mRNA were detected in the skin after dini trofluorobenzene challenge in normal mite, while this response was blu nted in CD28-/- mice, In addition, responses to irritant chemicals (cr oton oil and phenol) were also impaired in CD28-/- mice, IL-2, IFN-gam ma, and TNF-alpha mRNA levels were lower in CD28-/- mouse skin treated with phenol, T cells from CD28-/- mice did not bind to epidermal cell s derived from normal mice, while cocultivation of T cells with epider mal cells from normal mice demonstrated a significant binding, These r esults indicate that the CD28 molecule is required not only for optima l induction of allergic contact dermatitis, but also for the developme nt or irritant-induced skin inflammation. The expression of B7-1 and B 7-2 molecules on epidermal cells was induced by an allergen treatment in normal and CD28-/- mice, whereas only B7-2 was induced after irrita nt treatment, Lack of CD28 signaling may influence cutaneous inflammat ion by modulating skin cytokine profiles, possibly due to the decrease d contact of T cells with other cell populations expressing ligands fo r CD28. In addition, the results of this study suggest that allergic c ontact dermatitis and irritant dermatitis have overlapping pathophysio logic mechanisms, but subtle differences exist.