γδ T-APCs: a novel tool for immunotherapy?

The series of seminal articles in this book clearly illustrate the multi-functional nature of gamma delta T cells. Some of the functions correlate with the tissue tropism of distinct gamma delta T cell subsets whereas others appear to result from oligoclonal selection. Here, we discuss the antigen-presenting cell (APC) function of the major subset of circulating gamma delta T cells, V gamma 9/V delta 2 T cells, present in human blood. During tissue culture, V gamma 9/V delta 2 T cells uniformly respond to a class of non-peptide antigens, so-called prenyl pyrophosphates, derived from stressed host cells or from microbes. It is this feature that distinguishes human (and primate) V gamma 9/V delta 2 T cells from alpha beta and gamma delta T cells of all other species and that forms the basis for detailed studies of human V gamma 9/V delta 2 T cells. One of the consequences of V gamma 9/V delta 2 T cell activation is the rapid acquisition of APC characteristics (gamma delta T-APCs) reminiscent of mature dendritic cells (DCs). In the following discussion, we will discriminate between the potential use of gamma delta T-APCs as a cellular vaccine in immunotherapy and their role in anti-microbial immunity. Exploiting the APC function in gamma delta T-APCs represents a true novelty in current immunotherapy research and may lead to effective, anti-tumor immunity in cancer patients.