TCR γ/δ+ Dendritic Epidermal T Cells as Constituents of Skin-Associated Lymphoid Tissue

Abstract

The epidermis of all strains of normal mice is populated by two distinct dendritic, bone marrow-derived cells: Langerhans cells and CD4-CD8- Thy-1+ dendritic epidermal T cells (DETC). The overwhelming majority of DETC are an unusually homogeneous population of thymic-dependent cells which express CD3-associated T-cell antigen receptors (TCRs) of the gamma/delta type, thereby distinguishing them from conventional CD4+CD8- or CD4-CD8+ T cells expressing CD3-associated alpha/beta TCR. Most DETC are ontogenetically primitive, derived from early fetal thymocytes with a preferential, but poorly understood tropism for the epidermis. Like the TCR on other populations of gamma/delta cells, which preferentially populate other epithelia such as in the gut and lung, the TCR on most DETC selectively utilize particular variable (V) gene segments (i.e., V gamma 3 and V delta 1 for DETC vs V gamma 5 and V delta 4 or V delta 6 for intestinal intraepithelial lymphocytes). However, unlike other gamma/delta populations whose TCR junctional regions exhibit marked heterogeneity, DETC junctional diversity is extremely limited. This lack of TCR heterogeneity among DETC suggests they recognize a narrow range of physiologic ligands (antigens) and that this recognition is restricted not by conventional polymorphic class-I or class-II MHC molecules, but rather by relatively nonpolymorphic self MHC-like molecules of the class Ib MHC type [e.g., Qa, TL, and CD1 (T6)]. Additional studies are required to clarify precisely what DETC recognize, their relevant biological functions, as well as their relationship(s) to the gamma/delta cells recently identified in human skin.