It is believed that the size of the CD8

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.

We observed a significant increase in (CMV-specific) effector-type CD8 and CD4 T-cell counts in everolimus-treated patients. These findings may at least in part explain the reported low incidence of CMV-related pathology in everolimus-treated patients.

SummaryRabbit anti-thymocyte globulin (rATG) induces a long-lasting lymphocytopenia. CD4+ T cells remain depleted for up to 2 years, whereas the CD8 + T cell compartment is refilled rapidly by highly differentiated CD27 -CD45RA + CD57 + effector-type cells. Because the presence of these highly differentiated CD8+ T cells has been associated with cytomegalovirus (CMV) infection, we questioned to what extent restoration of CMV T cell immunity contributes to the re-emergence of T cells following rATG treatment. We compared T cell repopulation in six CMV-seropositive patients with CMV reactivation (reactivating CMV + ) to that in three CMV + patients without reactivation (non-reactivating CMV + ), and to that in three CMVseronegative recipients receiving a kidney from a CMV-seronegative donor (CMV -/-). All patients received rATG because of acute allograft rejection. Total CD4 and CD8 counts, frequency and phenotype of virus-specific CD8 + T cells were determined. In reactivating CMV + patients, total CD8 + T cells reappeared rapidly, whereas in non-reactivating CMV + patients they lagged behind. In CMV -/-patients, CD8 + T cell counts had not yet reached pretransplant levels after 2 years. CMV reactivation was indeed followed by a progressive accumulation of CMV-specific CD8 + T cells. During lymphocytopenia following rATG treatment, serum interleukin (IL)-7 levels were elevated. Although this was most prominent in the CMV-seronegative patients, it did not result in an advantage in T cell repopulation in these patients. Repopulated CD8 + T cells showed increased skewing in their Vb repertoire in both CMV -/-and reactivating CMV-seropositive patients. We conclude that rapid T cell repopulation following rATG treatment is driven mainly by CMV.