Molecular aspects of epithelial γδ T cell regulation

Abstract

γδ T cells lie at the interface between innate and adaptive immunity, sharing features with both arms of the immune system. The vast majority of γδ T cells reside in epithelial layers of tissues such as skin, gut, lung, tongue and reproductive tract where they provide a first line of defense against environmental attack. The existence of epithelium-resident γδ T cells has been known for over 20 years but our understanding of the molecular events regulating development and function of these cells is incomplete. We review recent advances in the field, with particular emphasis on the γδ T cell population resident in mouse epidermis. These studies have enhanced our knowledge and understanding of the life cycle of this enigmatic population of cells.

Figure 1

Molecular regulation of DETC development and function. DETC precursors develop in the fetal thymus from DN thymocytes by way of signals through Egr, Id3, ERK and Sox13. Subsequent maturation involves interaction with Skint1 expressed by thymic epithelial cells. It is unknown whether this interaction is directly through the TCR and whether TCR ligand is also required. Mature DETC precursors, upon exit from the thymus express low levels of CD24 and CCR6, but have increased CD122, CD44, S1P1 and KLF2 expression. These cells also require expression of CCR10 to migrate to the skin where they take up residence in the epidermal layer. Upon epidermal insult, DETC encounter with antigen expressed by damaged or malignant epithelial cells. DETC are activated through coordination of TCR and costimulatory signals, although the detailed nature of these signals remains under investigation. Subsequently, activated DETC are able to kill tumor cells or, alternatively, produce cytokines and growth factors, such as keratinocyte growth factor (KGF), to repair the damaged epithelial layer [53,62].