Phenotype and regulation of immunosuppressive Vδ2-expressing γδ T cells.

ABSTRACT

The proliferation and interleukin-2 production of CD4(+)CD25(-) αß T cells were inhibited in a cell-contact manner by Vδ2 γδ T cells. The transcription factor Helios was constitutively expressed in about one-third of circulating γδ 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 Vδ2 T cells and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on activated αß T cells mediated the suppression because the suppressive effect was abolished by blocking the CD86CTLA-4 interaction. Pre-treatment of Vδ2 T cells with Toll-like receptor 2 ligands enhanced phosphorylation of MAPKs, Akt, and NF-κB and partially abrogated the suppressive capacity, whereas on co-cultured responder T cells inhibitory molecules were downregulated and Akt and NF-κB phosphorylation was restored. Our results suggest that the regulation of αß T cell proliferation by activated Vδ2 T cells might contribute to fine-tuning of αß T cell responses.