Phenotype and regulation of immunosuppressive Vδ2-expressing γδ T cells

The proliferation and interleukin-2 production of CD4(+)CD25(-) alpha beta T cells were inhibited in a cell-contact manner by V delta 2 gamma delta T cells. The transcription factor Helios was constitutively expressed in about one-third of circulating gamma delta T cells and was upregulated by CD28-signaling. Our data suggest that Helios could serve as a marker for differential activation status rather than for regulatory T cells (Treg). Our findings also indicate that the interaction of CD86 on activated V delta 2 T cells and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on activated alpha beta T cells mediated the suppression because the suppressive effect was abolished by blocking the CD86:CTLA-4 interaction. Pre-treatment of V delta 2 T cells with Toll-like receptor 2 ligands enhanced phosphorylation of MAPKs, Akt, and NF-kappa B and partially abrogated the suppressive capacity, whereas on co-cultured responder T cells inhibitory molecules were downregulated and Akt and NF-kappa B phosphorylation was restored. Our results suggest that the regulation of alpha beta T cell proliferation by activated V delta 2 T cells might contribute to fine-tuning of alpha beta T cell responses.