Cutaneous biology of gammadelta T cells

The vast majority of serious noninfectious skin diseases are the result of inappropriate inflammatory responses (eg, atopic dermatitis, psoriasis) or neoplastic transformation (eg, squamous cell carcinoma, melanoma, cutaneous T-cell lymphoma). T cells are critical to both of these major disease categories, playing critical roles in driving or controlling inflammation, as well as the immunosurveillance of cutaneous tumors. T cells may express either 1 of 2 major T-cell receptor (TCR) subtypes composed of heterodimeric alphabeta or gammadelta proteins. While most T cells in the blood and lymph nodes are of the alphabeta type and demonstrate vast heterogeneity, gammadelta T cells are relatively enriched in epithelial tissues and often show less TCR variability. This distinction is especially evident in mice and several other mammals, as well as in humans, albeit to a lesser degree. Recent studies in laboratory animals have indicated the capacity of gammadelta T cells to play major roles in maintenance of the epidermal barrier, regulation of cutaneous inflammation, and protection against cutaneous neoplasms. This review will expound on the biology of gammadelta T cells, their relationship to the skin, and the implications for our understanding of cutaneous disease.