Fig. 6: ABHD11 influences human CD8+ T cell differentiation.
From: Lipoyl deglutarylation by ABHD11 regulates mitochondrial and T cell metabolism
a–d, Human CD8+ T cells were isolated from healthy donor peripheral blood mononuclear cells, activated with anti-CD3/CD28 Dynabeads, and continuously treated with 1 µM ML226 or 1 mM DM-2OG for 11 days. a, Timeline of treatment. Panel a is created with BioRender.com. b,c, CCR7 and CD45RO levels after 11 days were determined using flow cytometry. b, Representative flow cytometry dot plots. c, Percentage of CCR7highCD45ROhigh (central memory) and CCR7lowCD45ROhigh (effector memory). Each data point represents one donor. Mean ± s.d.; n = 5 donors; one-way ANOVA and Dunnett’s post-hoc test per subpopulation. d, CCR7, CD45RO, CD45RA, CD95, CD27 and CD28 levels after 11 days were determined using flow cytometry. Each data point represents one donor. Mean ± s.d., n = 5 donors, one-way ANOVA and Dunnett’s post hoc test. e, Following 11 days of culture with ML226, CD8+ T cells were counted, acclimatized to different oxygen tensions as indicated for 2 h, reactivated with anti-CD3/CD28 Dynabeads and cytokine levels in the media 4 h postreactivation were determined using a commercial multiplexed assay and flow cytometry. Mean ± s.d., n = 8 (IFNγ, FasL) and n = 4 (granzyme B) donors, two-way ANOVA and Dunnett’s post hoc test. f, Effect of ABHD11 inhibition on CD8+ T cells. ABHD11 inhibition reduces OGDHc activity via Lpglu accumulation on the OGDHc-E2. This results in impaired OXPHOS and is associated with a phenotypic switch to central memory CD8+ T cells, with reduced secretion of IFNγ and granzyme B under hypoxic conditions.
