Factors Involved in the Localization and Activation of Murine γδ Positive Dendritic Epidermal T Cells

Abstract

The vast majority of dendritic epidermal T cells (DETC) in normal mice express a monomorphic γδ-type T cell receptor (TCR) (V5JlCγl and V1D2J2Cδ coding segments, totally lacking junctional diversity). Cells with identical TCRs are also found in the early fetal thymus, but are not found in newborn or adult thymus, in peripheral lymphoid tissues or in other epithelial sites known to be populated by γδ cells expressing distinct receptors (e.g., in the gastrointestinal tract or in the reproductive tract). Early fetal thymocytes can serve as precursors for the DETC that populate adult skin; our recent adoptive transfer studies indicate an important role for cycling hair follicles in the localization and/or in situ proliferation of such precursors. The restricted tissue distribution and TCR homogeneity of DETC has suggested the possibility that the physiologic ligand for the DETC TCR is a common self-antigen expressed by keratinocytes or by other cells in their immediate microenvironment under a variety of potentially harmful circumstances (i.e., a stress protein). Recent in vitro data are consistent with this hypothesis: a DETC line was activated by exposure to stressed epidermal cells. Furthermore, increases in the densities of Vγ5/Vδl+ DETC in spontaneously depigmenting C57BL/6 vit/vit mice, in mice undergoing contact dermatitis reactions, and in normal mice during the neonatal period, all are consistent with the in situ activation/proliferation of DETC in response to a variety of pathologic and physiologic stimuli. It is now clear that human skin does not harbor a precise morphologic equivalent of mouse DETC. A number of persistent gaps in our knowledge about mouse DETC must be filled (including more precise identification of their physiologic ligand and their relevant functional roles in vivo), however, before we can really understand the relevance of mouse DETC to human cutaneous immunity and immunopathology.