Cross-presenting human γδ T cells induce robust CD8+ αβ T cell responses

γδ T cells are implicated in host defense against microbes and tumors but their mode of function remains largely unresolved. Here, we have investigated the ability of activated human Vγ9Vδ2+ T cells (termed γδ T-APCs) to cross-present microbial and tumor antigens to CD8+ αβ T cells. Although this process is thought to be mediated best by DCs, adoptive transfer of ex vivo antigen-loaded, human DCs during immunotherapy of cancer patients has shown limited success. We report that γδ T-APCs take up and process soluble proteins and induce proliferation, target cell killing and cytokine production responses in antigen-experienced and naive CD8+ αβ T cells. Induction of APC functions in Vγ9Vδ2+ T cells was accompanied by the up-regulation of costimulatory and MHC class I molecules. In contrast, the functional predominance of the immunoproteasome was a characteristic of γδ T cells irrespective of their state of activation. γδ T-APCs were more efficient in antigen cross-presentation than monocyte-derived DCs, which is in contrast to the strong induction of CD4+ αβ T cell responses by both types of APCs. Our study reveals unexpected properties of human γδ T-APCs in the induction of CD8+ αβ T effector cells, and justifies their further exploration in immunotherapy research.