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Correction: ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity

  • Meagan McMahon,
  • Siying Ye,
  • Leonard Izzard,
  • Daniel Dlugolenski,
  • Ralph A. Tripp,
  • Andrew G. D. Bean,
  • Daniel R. McCulloch,
  • John Stambas

Correction: ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity

  • Meagan McMahon, 
  • Siying Ye, 
  • Leonard Izzard, 
  • Daniel Dlugolenski, 
  • Ralph A. Tripp, 
  • Andrew G. D. Bean, 
  • Daniel R. McCulloch, 
  • John Stambas
PLOS
x

An influenza-specific CD8+ T cell peptide encoded within the nucleoprotein (NP) was incorrectly referred to as NP366-372 throughout the article. The correct designation should be NP366-374. The peptide sequence ASNENMETM stated throughout the ‘Methods’ section should also be attributed to NP366-374.

The authors have provided corrected versions of Fig 3, Fig 4, Fig 5, Fig 8, S10 Fig and S11 Fig.

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Fig 3. Reduced CD4+ and CD8+ T cell numbers in the spleens of influenza-infected Adamts5-/- mice.

C57.BL/6 and Adamts5-/- mice were intranasally (i.n.) infected (104 pfu/mouse) with X31 (H3N2) influenza virus. Spleens were removed at day 7 and day 10 p.i., and CD8+ T cell responses determined. Total CD4+ and CD8+ T cells numbers were calculated at days (A) 7 and (B) 10 p.i. Influenza-specific DbNP366-374 CD8+ and DbPA224-233 CD8+ tetramer-positive T cell numbers were measured at days (C) 7 and (D) 10 p.i. Functional influenza-specific DbNP366-374+IFNγ+CD8+ and DbPA224-233+IFNγ+CD8+ T cell activity was determined by ICS, and total IFNγ+ T cells enumerated at days (E) 7 and (F) 10 after infection. WT denotes C57.BL/6. The results are expressed as means ± SD, and statistical significance (relative to C57.BL/6) was determined by Student’s t test (*p ≤ 0.05, **p ≤ 0.01, n = 5 representing three experiments). Underlying data are provided in S1 Data.

https://doi.org/10.1371/journal.pbio.3000558.g001

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Fig 4. CD4+ and CD8+ T cell responses in the lungs of influenza-infected Adamts5-/- mice.

C57.BL/6 and Adamts5-/- mice were infected i.n. with 104pfu X31 (H3N2) influenza virus. Lungs were removed at days 7 and 10 p.i., and CD8+ T cell immunity characterised. Total CD4+ and CD8+ T cell numbers are shown at days (A) 7 and (B) 10 p.i. Influenza-specific tetramer+ DbNP366-374+ CD8+ and DbPA224-233+ CD8+ T cell responses were enumerated at days (C) 7 and (D) 10 p.i. CD8+ T cell functionality was assessed by ICS and DbNP366-374+IFNγ+CD8+ and DbPA224-233+IFNγ+CD8+ T cell responses enumerated at days (E) 7 and (F) 10 p.i. Wildtype denotes C57.BL/6 mice. The results are expressed as means ± SD, and statistical significance (relative to C57.BL/6) was determined by Student’s t test (* = p ≤ 0.05, ** = p ≤ 0.01, n = 5 representing three experiments). Underlying data are provided in S1 Data.

https://doi.org/10.1371/journal.pbio.3000558.g002

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Fig 5. T cell immunity in the pooled MLN.

C57.BL/6 and Adamts5-/- mice were infected i.n. with 104 pfu/mouse X31 (H3N2) influenza virus. MLNs were removed, pooled, and processed at days 7 and 10 p.i., and single-cell suspensions analysed for influenza-specific immunity. Total CD4+ and CD8+ T cell numbers were determined at days (A) 7 and (B) 10 p.i. Influenza-specific DbNP366-374+ CD8+ and DbPA224-233+ CD8+ tetramer positive T cells were enumerated at days (C) 7 and (D) 10 p.i. CD8+ T cell functionality was measured using ICS. Influenza-specific DbNP366-374+IFNγ+CD8+ and DbPA224-233+IFNγ+CD8+ T cell responses were characterised at days (E) 7 and (F) 10 p.i. Results are expressed as total pooled means from five mice repeated three times. Wildtype denotes C57.BL/6 mice. Underlying data are provided in S1 Data.

https://doi.org/10.1371/journal.pbio.3000558.g003

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Fig 8. Versican reduction in Adamts5-/-Vcan+/hdf mice restores normal T cell function.

Spleen and MLNs were removed from C57.BL/6, Adamts5-/-Vcan+/+, and Adamts5-/-Vcan+/hdf mice and processed at day 10 p.i., and single cell suspensions were analysed for influenza-specific immunity. (A) Total CD8+ T cell numbers were determined at day 10 p.i. in the spleen. (B) Influenza-specific DbNP366-374+ CD8+ and DbPA224-233+ CD8+ tetramer positive T cells in the spleen were enumerated at day 10 p.i. CD8+ T cell functionality was measured using ICS. (C) Influenza specific DbNP366-374+IFNγ+CD8+ and DbPA224-233+IFNγ+CD8+ T cell responses were characterised in the spleen at days 10 p.i. (D) Total CD8+ T cell numbers were assessed at day 10 p.i. in the pooled MLN. (E) Influenza-specific DbNP366-374+ CD8+ and DbPA224-233+ CD8+ tetramer positive T cells in the pooled MLN were enumerated at day 10 p.i. CD8+ T cell functionality was measured using ICS. (F) Influenza-specific DbNP366-374+IFNγ+CD8+ and DbPA224-233+IFNγ+CD8+ T cell responses were characterised in the pooled MLN at day 10 p.i. The results are expressed as means ± SD (spleen data) or as pooled means (MLN data), and statistical significance (relative to C57.BL/6 mice) was determined by one-way ANOVA (*p ≤ 0.05, ***p ≤ 0.005 relative to C57.BL/6, n = 5 representing three individual experiments). WT denotes C57.BL/6 mice and ts5-/- denotes Adamts5-/-. (G) Our model for ADAMTS5 enzyme activity and T cell migration proposes that versican can inhibit T cell effector function by acting as a physical block. Cleavage of versican by ADAMTS5 removes the ECM blockade, allowing migration (top panel). Moreover, versican accumulation in the absence of ADAMTS enzyme activity results in T cell clustering (bottom panel). Underlying data are provided in S1 Data.

https://doi.org/10.1371/journal.pbio.3000558.g004

The relevant figure legends have been amended to reflect this change and are presented below.

Supporting information

S10 Fig. Influenza virus infection of Vcan+/hdf mice.

Lung tissue and MLNs were removed from influenza virus infection C57.BL/6 and Vcan+/hdf mice and processed to generate single cell suspensions at day 10 p.i. for analysis of influenza-specific immunity. (A) Total CD8+ T cell numbers were determined at day 10 p.i. in the lung. (B) Influenza-specific DbNP366-374+ CD8+ and DbPA224-233+ CD8+ tetramer positive T cells in the lung were enumerated at day 10 p.i. CD8+ T cell functionality was measured using ICS. (C) Influenza specific DbNP366-374+IFNγ+CD8+ and DbPA224-233+IFNγ+CD8+ T cell responses were characterised in the lung at day 10 p.i. (D) Total CD8+ T cell numbers were determined at day 10 p.i. from pooled MLN samples. (E) Influenza-specific DbNP366-374+ CD8+ and DbPA224-233+ CD8+ tetramer positive T cells in pooled MLN were enumerated at day 10 p.i. (F) CD8+ T cell functionality was measured using ICS to assess influenza-specific DbNP366-374+IFNγ+CD8+ and DbPA224-233+IFNγ+CD8+ T cell responses at day 10 p.i. The results are expressed as means ± SD or as pooled means (MLN data) and statistical significance (relative to C57.BL/6 mice) determined by a Student’s t test (*p ≤ 0.05, ***p ≤ 0.005 relative to C57.BL/6, n = 5 representing three individual experiments). WT denotes C57.BL/6 mice. Underlying data are provided in S2 Data.

https://doi.org/10.1371/journal.pbio.3000558.s001

(TIF)

S11 Fig. Influenza infection of Adamts5-/- and WT littermate controls.

Adamts5-/- and WT mice were infected i.n with X31 (H3N2) influenza virus and spleens, lungs, and MLNs removed from C57.BL/6 and Adamts5-/- mice days 7 p.i. Single cell suspensions were then analysed for influenza-specific immunity. (A) Weight loss was calculated over the time course of infection. Total CD4+ and CD8+ T cells were enumerated in the (B) spleen, (C) lung, and (D) MLN. Influenza-specific DbNP366-374+ CD8+ and DbPA224-233+ CD8+ tetramer positive T cell numbers were also characterised in the (B) spleen, (C) lung, and (D) MLN. Lung and spleen results are expressed as means ± SD or as pooled means (MLN data), and statistical significance (relative to C57.BL/6 mice) was determined by a Student’s t test (*p ≤ 0.05, **p ≤ 0.01 relative to C57.BL/6 mice, n = 5 representing three individual experiments). WT denotes C57.BL/6 mice. Underlying data are provided in S2 Data.

https://doi.org/10.1371/journal.pbio.3000558.s002

(TIF)

Reference

  1. 1. McMahon M, Ye S, Izzard L, Dlugolenski D, Tripp RA, Bean AGD, et al. (2016) ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity. PLoS Biol 14(11): e1002580. https://doi.org/10.1371/journal.pbio.1002580 pmid:27855162