ABCB10 Loss Reduces CD4 T Cell Activation and Memory Formation.

T cells must shift their metabolism to respond to infections and tumors and to undergo memory formation. The ATP-binding cassette transporter ABCB10 localizes to the mitochondrial inner membrane, where it is thought to export a substrate important in heme biosynthesis and metabolism, but its role in T cell development and activation is unknown. In this article, we use a combination of methods to study the effect of ABCB10 loss in primary and malignantly transformed T cells. Although is dispensable for development of both CD4 and CD8 T cells, it is required for expression of specific cytokines in CD4, but not CD8, T cells activated in vitro. These defects in cytokine expression are magnified on repeated stimulation. In vivo, CD8 cells lacking ABCB10 expand more in response to viral infection than their control counterparts, while CD4 cells show reductions in both number and percentage. CD4 cells lacking ABCB10 show impairment in Ag-specific memory formation and recall responses that become more severe with time. In malignant human CD4 Jurkat T cells, we find that CRISPR-mediated disruption recapitulates the same cytokine expression defects upon activation as observed in primary mouse T cells. Mechanistically, deletion in Jurkat T cells disrupts the ability to switch to aerobic glycolysis upon activation. Cumulatively, these results show that ABCB10 is selectively required for specific cytokine responses and memory formation in CD4 T cells, suggesting that targeting this molecule could be used to mitigate aberrant T cell activation.