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. Author manuscript; available in PMC: 2014 May 1.
Published in final edited form as: Nat Immunol. 2013 Sep 29;14(11):1173–1182. doi: 10.1038/ni.2714

Figure 1.

Figure 1

VHL-deficient CD8+ T cells mediate HIF-1α–HIF-2α–dependent death during persistent viral infection. (a) Survival of wild-type (Vhlfl/fl) mice (WT) or VHL-deficient (Vhlfl/fldLck) mice (VHL-KO) after acute infection with LCMV Armstrong (+ Arm) or chronic infection with LCMV clone 13 (+ cl13) (far left) and core body temperature of those mice after chronic infection with LCMV clone 13 (middle left), as well as survival (middle right) and core body temperature (far right) of wild-type host mice given ~1 × 104 VHL-sufficient (WT) or VHL-deficient (VHL-KO) P14 CD8+ T cells (P14→WT), then infected 1 d later as at left. Pooled sample size (host mice): survival (left), n = 15 (wild type) or 11 (VHL-deficient); survival (right), n = 9 (wild-type cells) or 9 (VHL-deficient cells); body temperature, n ≥ 3 per time point. *P =0.003 and **P < 0.001, wild-type versus mutant during chronic infection (log-rank (Mantel-Cox) test). (b) Perimortal lung pathology in wild-type host mice (n = 4) given no cells and left uninfected (UI) or given 1 × 104 VHL-sufficient P14 CD8+ T cells (WT P14→WT) or VHL-deficient P14 CD8+ T cells (VHL-KO P14→WT), then infected 1 d later with LCMV clone 13 and assessed 9 d later. Scale bar, 100 μm. (c) Immunoblot analysis of HIF-1α, HIF-2α and lamin B (loading control throughout) in nuclear extracts of purified wild-type, VHL-deficient (VHL-KO), Hif1afl/flCd4-Cre (HIF-1α-KO) or Epas1fl/flTie2-Cre (HIF-2α-KO) CD8+ T cells left unstimulated (US) or activated for 55 h in vitro with anti-CD3 plus anti-CD28. (d) Survival and core body temperature as in a, but with wild-type and VHL–HIF-1α–HIF-2α-deficient (VHL–HIF-1α–HIF-2α-KO) mice (left) or in wild-type hosts after transfer of wild-type P14 or VHL–HIF-1α–HIF-2α-deficient P14 cells (P14WT; right). Pooled sample size (mice): survival (left), n = 3 (wild type) or 3 (VHL–HIF-1α–HIF-2α-deficient); survival (right), n = 5 (wild-type cells) or 8 (VHL–HIF-1α–HIF-2α-deficient cells); body temperature, n ≥ 3 mice per time point. Data are pooled from three experiments (a,d; error bars, s.e.m.) or are representative of two experiments (b,c).