Cross-talk between intraepithelial γδ T cells and epithelial cells

Abstract

Intraepithelial γδ T cells play pivotal roles in homeostasis, tissue repair, inflammation, and protection from malignancy. In some tissues, γδ T cells are the only resident T cell population, whereas in others, they coexist with αβ T cells and other lymphocyte populations. γδ T cell function in the epithelium requires constant communication between cells in the form of cell-to-cell contacts and cell-to-matrix interactions. These interactions coordinate with the timely production of specific cytokines, chemokines, growth factors, and glycosaminoglycans, which have specialized effects on neighboring epithelial cells. Antigens that activate these T cells are not well-defined, and they do not express classic costimulatory or coreceptor molecules. As such, an understanding of the mechanisms used by epithelial γδ T cells to maintain homeostasis and facilitate wound repair has necessitated the identification of novel molecular interactions between γδ T cells and their neighboring epithelial cells.

Keywords: dendritic epidermal T cells; epithelium; lymphocytes; wound repair.

Figure 1.. DETC are in constant contact with neighboring keratinocytes, surveying for signs of damage or disease.

Epidermal sheets from a WT mouse were stained with anti-γδ TCR mAb (green fluorescence) to visualize DETC and DAPI (blue nuclei) to visualize keratinocytes. Each DETC can simultaneously contact multiple keratinocytes through dendritic processes.

Figure 2.. Cross-talk in epidermal γδ T cell activation.

γδ DETC recognize stress or damage signals delivered by keratinocytes. This recognition involves the coordinated interaction between the TCR and its unknown ligand, together with the costimulatory molecules, JAML and NKG2D, with their keratinocyte ligands, CAR and H60c/RAE 1, respectively. Additional signals are generated through CD100 on DETC and plexin B2 on keratinocytes to initiate DETC rounding prior to complete activation. Activated DETC exhibit a round morphology and secrete KGFs (KGF-1 and KGF-2) that facilitate keratinocyte proliferation and re-epithelialization. Simultaneous secretion of a battery of cytokines and chemokines ensures an appropriate effector response and recruitment of inflammatory cells. Together, these coordinated events allow the efficient functioning of all facets of the wound-repair process.