Fig. 3: Ancestral and VOC SARS-CoV-2 elicit immune responses in the lungs of mice.

a, T cells from lungs of infected mice (n = 3) were phenotypically distinct and expressed PD1. Single-cell suspensions of lungs from mock-infected and WA1-infected K18-hACE2 mice were harvested at 9 d.p.i. and analysed by CyTOF. Shown are tSNE plots gated on total immune cells (CD45⁺) from the lungs of mice, coloured by expression levels of the antigen listed at the top (red shows the highest expression and blue represents the lowest expression). 'Islands' of CD4⁺ and CD8⁺ T cells unique to the infected mice (identified by green and purple arrows, respectively, in the third row) express especially high levels of the activation/exhaustion marker PD1, as demonstrated in the right-hand column. b,c, T cells from lungs of infected mice (n = 3) expressed elevated levels of the activation/checkpoint antigens PD1 and CTLA4. The proportions of CD4⁺ (b) and CD8⁺ (c) T cells expressing PD1, CTLA4 or both PD1 and CTLA4 are indicated. d, SARS-CoV-2-specific T cells are elicited in the lungs of mice infected with SARS-CoV-2. Representative plots corresponding to pulmonary T cells from uninfected (mock) and WA1-infected K18-hACE2 mice, stimulated for 6 h with or without overlapping SARS-CoV-2 spike peptides. Note that SARS-CoV-2-specific T cells (those producing IFNγ and/or TNF) were only detected in infected mice after peptide stimulation (n = 3). e,f, SARS-CoV-2-specific T cells are elicited in the lungs of mice infected with WA1 (n = 6), Delta (n = 3) and Omicron (n = 3). The proportions of CD4⁺ (e) and CD8⁺ (f) T cells expressing IFNγ and/or TNF (gated as shown in c) are indicated. CD4⁺ T cell responses trended highest in Delta-infected mice, and the CD8⁺ T cell responses were highest in Delta-infected and Omicron-infected mice (n = 3). In b,c,e,f, data are shown as the average ± s.e.m. analysed by the two-tailed unpaired Student’s t-test.

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