Immunobiology of mouse dendritic epidermal T cells: a decade later, some answers, but still more questions.

Over the past decade, overwhelming evidence has accumulated in many species, most notably in mice, that epithelial sites such as skin, intestine, and reproductive tract are populated with relatively discrete subsets of gamma delta cells. Such studies have identified several distinguishing and, in some cases, unique features of the dendritic epidermal T cells (DETC) populating the skin of all normal mice: homogeneous V5-J1-C gamma 1/V1-D2-J2-C delta T-cell receptors devoid of junctional diversity, apparent tissue restriction in adult mice to the skin, an important role for active hair growth in their localization and/or proliferation in the skin, and a capacity to recognize an antigen expressed on stressed epidermal cells. These properties have led to the hypothesis that DETC play distinctive roles in cutaneous immune surveillance and/or immunoregulation via recognition of a common self-antigen expressed by adjacent cells under various potentially harmful circumstances. Despite substantive advances in our knowledge about gamma delta cells in general (e.g., recent evidence that their manner of antigen recognition may be fundamentally different from that used by conventional alpha beta T cells) and about epithelial-specific subsets such as murine DETC in particular, it is clear that, compared with our understanding of alpha beta cells, major gaps still exist in our understanding of these cells. Persisting questions about DETC include: precise identification of the ligands for their homogenous T-cell receptors, the cellular and molecular requirements for their activation, their full range of functional activities, the reason(s) for the absence in normal human skin of a precise morphologic and phenotypic homologue, and, perhaps most important, their biologically relevant role(s) in cutaneous physiology, immunity, and/or pathology.