TCR γ δ⁺ dendritic epidermal T cells as constituents of skin-associated lymphoid tissue

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 γ/δ type, thereby distinguishing them from conventional CD4⁺CD8^- or CD4^-CD8⁺ T cells expressing CD3-associated α/β 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 γ/δ 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., Vγ3 and Vδ1 for DETC vs Vγ5 and Vδ4 or Vδ6 for intestinal intraepithelial lymphocytes). However, unlike other γ/δ 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 CD 1 (T6)]. Additional studies are required to clarify precisely what DETC recognize, their relevant biological functions, as well as their relationship(s) to the γ/δ cells recently identified in human skin.