Extended Data Fig. 7: Critical role of CD8+ T cells in severe disease.
(a) Experimental setup. Ab- DHLMP2a mice were infected with a target dose of 5 × 104 TCID50 of rSARS-CoV-2-N501YMA30 through aerosol exposure. Thirty days after infection, primed mice were exposed to a heterologous challenge with a target dose of 1x105 TCID50 of rSARS-CoV-2-N501YMA30. Ab− (n = 4) naïve mice unexposed to the primary challenge were infected with 1x105 TCID50 of rSARS-CoV-2-N501YMA30. A group of primed mice was injected intravenously with anti-CD4 (n = 4), or anti-CD8 (n = 4), or the combination of anti-CD4 and anti-CD8 (n = 5) depleting antibodies three (day 27) and one day (day 29) prior to re-infection and three days later (day 33). Non-infected mice exposed to aerosolized PBS were used as control. Analyses were performed 4 days post re-challenge. (b) Quantification of SARS-CoV-2 RNA in the nasal turbinates of the indicated mice. n as indicated in a. RNA values are expressed as copy number per ng of total RNA and the limit of detection is indicated as a dotted line. (c) Representative immunohistochemical micrographs of lung sections from indicated mice. N-SARS-CoV-2 positive cells are depicted in brown. Scale bars, 100 μm. Data are expressed as mean ± SEM and are representative of two independent experiments. *p value < 0.05, **p value < 0.01; Kruskal-Wallis test followed by uncorrected Dunn’s test, each comparison stands alone (b).
