miR 625 3p is upregulated in CD8+ T cells during early immune reconstitution after allogeneic stem cell transplantation
Alloreactive CD8+ T cells mediate the curative graft versus leukaemia effect, the anti viral immunity and graft versus host disease (GvHD) after allogeneic stem cell transplantation (SCT) Thus, immune reconstitution with CD8+ T cells is critical for the outcome of patients after allogeneic SCT. Certain miRNAs such as miR 146a or miR 155 play an important role in the regulation of post transplant immunity in mice. While some miRNAs e.g. miR 423 or miR 155 are regulated in plasma or full blood during acute GvHD also in man, the relevance and expression profile of miRNAs in T cells after allogeneic SCT is unknown. miR 625 3p has recently been described to be overexpressed in colorectal malignancies where it promotes migration, invasion and apoptosis resistance. Since similar regulative functions in cancer and T cells have been described for an increasing number of miRNAs, we assumed a role for the cancer related miR 625 3p also in T cells. Here, we studied miR 625 3p expression selectively in CD8+ T cells both in vitro and during immune reconstitution after allogeneic SCT in man. T cell receptor stimulation lead to miR 625 3p upregulation in human CD8+ T cells in vitro. Maintenance of elevated miR 625 3p expression levels was dependent on ongoing T cell proliferation and was abrogated by withdrawal of interleukin 2 or the mTOR inhibitor rapamycin. Finally, miR 625 3p expression was analyzed in human CD8+ T cells purified from 137 peripheral blood samples longitudinally collected from 74 patients after allogeneic SCT. miR 625 3p expression was upregulated on day 25 and on day 45, i.e. during the early phase of CD8+ T cell reconstitution after allogeneic SCT and subsequently declined with completion of CD8+ T cell reconstitution until day 150. In conclusion, this study has shown for the first time that miR 625 3p is regulated in CD8+ T cells during proliferation in vitro and during early immune reconstitution after allogeneic SCT in vivo. These results warrant further studies to identify the targets and function of miR 625 3p in CD8+ T cells and to analyze its predictive value for an effective immune reconstitution.
PloS one