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 Abcb10 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 ABCB10 disruption recapitulates the same cytokine expression defects upon activation as observed in primary mouse T cells. Mechanistically, ABCB10 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.