γδ T cell migration: Separating trafficking from surveillance behaviors at barrier surfaces

Abstract

γδ T cells are found in highest numbers at barrier surfaces throughout the body, including the skin, intestine, lung, gingiva, and uterus. Under homeostatic conditions, γδ T cells provide immune surveillance of the epidermis, intestinal, and oral mucosa, whereas the presence of pathogenic microorganisms in the dermis or lungs elicits a robust γδ17 response to clear the infection. Although T cell migration is most frequently defined in the context of trafficking, analysis of specific migratory behaviors of lymphocytes within the tissue microenvironment can provide valuable insight into their function. Intravital imaging and computational analyses have been used to define "search" behavior associated with conventional αβ T cells; however, based on the known role of γδ T cells as immune sentinels at barrier surfaces and their TCR-independent functions, we put forth the need to classify distinct migratory patterns that reflect the surveillance capacity of these unconventional lymphocytes. This review will focus on how γδ T cells traffic to various barrier surfaces and how recent investigation into their migratory behavior has provided unique insight into the contribution of γδ T cells to barrier immunity.

Keywords: immune surveillance; migration; mucosal immunity; γδ T cells.

Figure 1.. Surveillance behaviors of γδ IELs.

Under homeostatic conditions, γδ IELs exhibit a flossing behavior in which the cells migrate along the basement membrane and into the lateral intercellular space (LIS). In the absence of commensal bacteria, migration into the LIS is ablated resulting in continuous migration along the basolateral aspect of the epithelium (surveying). γδ IELs may not fully enter the LIS but instead extend projections between adjacent IECs (probing). Inhibiting IL-2Rβ/PI3K signaling results in an idling behavior characterized by an inability of γδ IELs to effectively polarize and migrate out of the LIS

Figure 2.. Ligand-binding interactions involved in regulating γδ IEL surveillance behavior.

Homotypic interactions between epithelial and γδ IEL occludin are required for IEL motility. CD103 (αEβ7 integrin) binding to epithelial E-cadherin functions as a retention signal within the LIS. Activation of IL-2Rβ by epithelial IL-15/IL-15Rα complexes promotes γδ IEL motility and maintains γδ T cell localization within the epithelial compartment