William A. Kuziel

Effect of Keratinocyte Cytokines on Thy‐1+ Dendritic Epidermal Cells

It is now well recognized that the epidermis of normal mice contains two distinct populations of dendritic, bone marrow-derived cells; Ia+ Langerhans cells and Thy1 + epidermal cells (Thy-1 + EC). Particularly during the past two years, knowledge about Thy-1 + EC has advanced to the point that these cells are of considerable interest to a variety of investigators including cellular and molecular immunologists and cutaneous biologists. It has become apparent that Thy-1 + EC are a readily accessible and perhaps unusually homogeneous population with the genotypic, phenotypic, and functional properties of a newly identified subset of T lymphocytes which express a y/S T cell antigen receptor (TCR), whose relationships to other T cells are just beginning to be understood, and whose relevant in vivo roles have yet to be defined. Thy-l+ EC normally are found distributed in a fairly regular and dendritic array throughout interfollicular epithelium as well as in a somewhat less uniform pattern within follicular epithelium, putting them in direct contact with large numbers of keratinocytes. This localization, when coupled with our rapidly advancing understanding that keratinocytes are a rich source of cytokines capable of affecting the growth, differentiation and state of activation of a variety of lymphoid cells, raises obvious questions about the effects of such cytokines on Thy-I + EC. Available evidence gives rise to the intriguing possibility that some, if not all, steps in the differentiation of bone marrow-derived, immature, CD3TCRprecursors into CD3+ TCR y/6+ T cells may occur within the epidermis, thereby implicating keratinocytes and/or their cytokines in that process. Furthermore, data are consistent with the possibility that epidermal keratinocytes may provide accessory signals necessary for mitogen-driven proliferation of Thy-l+ EC in vitro. Finally, some populations of activated Thy-I+ EC, under appropriate circumstances, can utilize known or presumed keratinocyte cytokines as growth factors. This paper will summarize these recent data in the context of our present understanding of the phenotypic, genotypic, and functional characteristics of Thy-1 + EC and their relationship(s) to other T lymphocytes.