A comprehensive review of the phenotype and function of antigen-specific immunoregulatory double negative T cells

Double negative T cells that lack the expression of both CD4 and CD8 T cell co-receptors exhibit a most unique antigen-specific immunoregulatory potential first described over a decade ago. Due to their immunoregulatory function, this rare T cell population has been studied in both mice and humans for their contribution to peripheral tolerance and disease prevention. Consequently, double negative cells are gaining interest as a potential cellular therapeutic. Herein, we review the phenotype and function of double negative T cells with emphasis on their capacity to induce antigen-specific immune tolerance. While the phenotypic and functional similarities between double negative T cells identified in mouse and humans are highlighted, we also call attention to the need for a specific marker of double negative T cells, which will facilitate future studies in humans. Altogether, due to their unique properties, double negative T cells present a promising therapeutic potential in the context of various disease settings.

► Immunoregulatory DN T cells present a unique antigen-specific mode of tolerance.
► A major challenge remains the identification of unique markers for these cells.
► Human DN T cells present a promising avenue in cell therapy.