In vivo activation of Langerhans cells and dendritic epidermal T cells in the elicitation phase of murine contact hypersensitivity

Langerhans cells (LCs) and dendritic epidermal T cells (DETCs) constitute t he skin immune system. To demonstrate:the kinetics of in vivo activation of murine LCs and DETCs in the elicitation phase of contact hypersensitivity, we measured the cell area positively stained for I-A and gamma delta T-cel l receptor (or Thy-1.2), respectively, under a fluorescence microscope at v arious time intervals after topical application of dinitrofluorobenzene. Th e fluorescence-positive area of LCs increased in parallel with that of DETC s at 1 h and 24 h, indicating the biphasic activation of LCs and DETCs. Ear ly activation was hapten-specific and often exhibited close LC-to-DETC appo sition. Experiments with in vivo administration of neutralizing anticytokin e antibodies revealed that none of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 beta were involved in the inducti on of early activation of LCs and DETCs, while TNF-alpha and IL-1 beta medi ated late activation of LCs, and IFN-gamma and IL-1 beta mediated that of D ETCs. Our results indicate that LCs and DETCs are synchronously and biphasi cally activated in the epidermis during the elicitation phase of contact hy persensitivity and suggest that different mechanisms may control early and late activation.