Features and functions of gamma delta T lymphocytes: focus on chemokines and their receptors

gamma delta T cells are a distinct subgroup of T lymphocytes that are enriched at certain anatomical localizations, such as the small intestinal epithelia and other epithelia. gamma delta T cells recognize microbial antigens, such as heat shock proteins (in mice) or phosphorylated bacterial metabolites (in humans), and control the integrity of epithelia. At the effector cell level, they share with the conventional alpha beta T lymphocytes potent cytotoxic activity and the capacity to produce a variety of cytokines, including specific cytokines such as keratinocyte growth factor. Here we summarize the current knowledge on the role of chemokines and their receptors in the migration and function of gamma delta T cells. As an example, the migration of gamma delta T cells to the small intestine is guided by the chemokine receptor CCR9 and the local expression of the corresponding ligand CCL25 (also termed thymus-expressed chemokine, TECK). Chemokine receptor expression also correlates with the functional program of T cells. In this respect, the strong expression of the MIP-1 alpha/MIP-1 beta/RANTES (CCL3/CCL4/CCL5)-receptor CCR5 correlates with a T-helper 1 phenotype of human V gamma 9V delta 2-expressing gamma delta T cells. The regulation of chemokine receptors, together with the pattern of local chemokine production, plays an important role in the localization of gamma delta T cells under physiological and pathophysiological conditions, such as infection, inflammation, and tumor defense.