Endothelial activation in cell mediated reactions: cellular and molecular reactions involved in tissue damage.

T cell lines specific for hapten trinitrochlorobenzene (TNP) were obtained from mice immunized epicutaneously by repeated in vitro stimulation of lymph node cells, with the specific antigen and IL-2. These cell lines, although producing typical Th1 cytokines (IL-2, IL-3, TNFα and IFN-γ) failed to transfer systemically (i.e. when given intravenously) a delayed-type hypersensitivity (DTH) reaction. A successful transfer of DTH was obtained when the recipient mice were injected in vivo with IL-4 or the cell lines were incubated in vitro with IL-4. Dose-response analysis revealed that as few as 10 pg IL-4 were effective. Time-course studies showed that IL-4 allowed a successfull systemic transfer of DTH when injected in vivo 2 hours before or at the same time as the injection of the cell lines, but not when given later on. As the cell lines fail to transfer DTH when given i.v. but mediate DTH when injected, together with antigen, at the challenge site, the strong likelyhood is that they fail to migrate from the blood stream to the site of challenge. Therefore, it is likely that IL-4 allows cell lines to transfer systemically DTH by inducing the expression of critical adhesion molecules on endothelial cells which permit localization of antigen-specific cells at the site of antigen deposition.