Analysis of stem-cell-like properties of human CD161++IL-18Rα+ memory CD8+ T cells

Abstract

CD161(++)IL-18Rα(+)CD8(+) human T cells have recently been identified as a new subset of memory cells but their exact role remains unclear. CD161(++)IL-18Rα(+)CD8(+), mucosal-associated invariant T cells express a semi-invariant TCR Vα7.2-Jα33, which recognizes the MHC-related protein 1. On the basis of properties including the expression of the ABC-B1 transporter, cKit expression and survival after chemotherapy, CD161(++)IL-18Rα(+)CD8(+) T cells have been designated as 'stem' cells. Here we analyse location and functional properties of CD161(++)IL-18Rα(+) CD8(+) T cells and question whether they have other traits that would mark them as genuine 'stem' cells. CD161(++)IL-18Rα(+)CD8(+) T cells were found in peripheral blood, spleen and bone marrow but interestingly hardly at all in lymph nodes (LNs), which may possibly be explained by the finding that these cells express a specific set of chemokine receptors that allows migration to inflamed tissue rather than to LNs. In addition to TCR ligation and co-stimulation, CD161(++)IL-18Rα(+) CD8(+) T cells require cytokines for proliferation. The CD161(++)IL-18Rα(+) CD8(+) pool contains cells reactive towards peptides, derived from both persisting and cleared viruses. Although CD161(++)IL-18Rα(+) CD8(+) T cells express the ABC-B1 transporter, they have shorter telomeres and less telomerase activity and do not express aldehyde dehydrogenase. Finally, CD161(++)IL-18Rα(+) CD8(+) T cells show similarities to terminally differentiated T cells, expressing IFNγ, KLRG1 and the transcription factor Blimp-1. In conclusion, CD161(++)IL-18Rα(+) CD8(+) T cells lack many features of typical 'stem' cells, but appear rather to be a subset of effector-type cells.