gamma delta T Cells and Their Potential for Immunotherapy

V gamma 9V delta 2 (also termed V gamma 2V delta 2) T cells, a major human peripheral blood gamma delta T cell subset, recognize microbial (E)-4-hydroxy-3-methylbut-2-enyl diphosphate and endogenous isopentenyl diphosphate in a TCR-dependent manner. The recognition does not require specific accessory cells, antigen uptake, antigen processing, or MHC class I, class II, or class Ib expression. This subset of T cells plays important roles in mediating innate immunity against a wide variety of infections and displays potent and broad cytotoxic activity against human tumor cells. Because gamma delta T cells express both natural killer receptors such as NKG2D and gamma delta T cell receptors, they are considered to represent a link between innate and adaptive immunity. In addition, activated gamma delta T cells express a high level of antigen-presenting cell-related molecules and can present peptide antigens derived from destructed cells to alpha beta T cells. Utilizing these antimicrobial and anti-tumor properties of gamma delta T cells, preclinical and clinical trials have been conducted to develop novel immunotherapies for infections and malignancies. Here, we review the immunological properties of gamma delta T cells including the underlying recognition mechanism of nonpeptitde antigens and summarize the results of gamma delta T cell-based therapies so far performed. Based on the results of the reported trials, gamma delta T cells appear to be a promising tool for novel immunotherapies against certain types of diseases.