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ScRNA-seq analyses on Thy1.1+Thy1.2+ MDR1-sufficient and Thy1.1+Thy1.2- MDR1-deficient P14 CD8+ T cells from ten congenically-transferred and LCMV-infected wild type B6 mice at day 8 post-infection

ABSTRACT: Multidrug resistance (MDR)-1 acts as a chemotherapeutic drug efflux pump in tumor cells, although its physiologic functions remain enigmatic. Using a recently-developed MDR1-knockin reporter allele (Abcb1aAME/+), we found that constitutive MDR1 expression amongst hematopoietic cells was observed mainly in cytolytic lymphocytes—including CD8+ cytotoxic T lymphocytes (CTL) and natural killer cells—and regulated by Runt-related (Runx) transcription factors. Although MDR1 was dispensable for naïve CD8+ T cell development, it was required for both normal accumulation of effector CTL following acute viral infection and protective function of memory CTL upon challenge with an intracellular bacterium. MDR1 acted early after naïve CD8+ T cell activation to suppress oxidative stress, enforce survival and safeguard mitochondrial function in developing CTL. Together, these data highlight an important endogenous function of MDR1 in cell-mediated immune responses, and suggest that ongoing efforts to intentionally inhibit MDR1 in cancer patients could be counter-productive.

ORGANISM(S): Mus musculus

PROVIDER: GSE143140 | GEO | 2020/02/28

REPOSITORIES: GEO

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