Fig. 5. HCMV re-exposure further promotes antibody induction and class switching and boosts HCMV-specific T-cell responses in BLT-L mice.

a,b, HCMV-specific IgM (a) and IgG (b) in naïve BLT-L mice (n = 5) and following single or 3–4 exposures to HCMV TB40/E (IgM n = 15 single and 11 re-exposed mice, IgG n = 4 single and 11 re-exposed mice) or AD169 (IgM n = 8 single and 13 re-exposed mice, IgG n = 4 single and 11 re-exposed mice). Negative (open diamonds) and positive (filled diamonds) standards (STD). Shown is the mean of three technical replicates per mouse. Dashed line, threshold for seropositivity defined from naïve controls. c, HCMV re-exposure induced IE1-specific TNF-α/IFN-γ double positive CD4⁺ T cells at the site of inoculation, the human lung implant and systemically in the liver. Contour plots exampling HCMV-IE1-specific CD8⁺ T-cell IFN-γ production and CD107a degranulation in a BLT-L mouse. d, CD8⁺ T cells were isolated from combined tissues of TB40/E (top panels representative of measurements in 4 independent BLT-L mice) or AD169 (bottom panels representative of measurements in 11 independent BLT-L mice) exposed mice, stimulated and then assessed using ICS. e, Summary graph showing background subtracted IE1-specific CD8⁺ T-cell responses (IFN-γ production) in mice receiving repeated inoculations of TB40/E or AD169. Filled symbols show positive responses and open symbols indicate negative responses. TB40/E open squares and circles represent mice in cohorts D and F, respectively; AD169 open squares and circles represent mice in cohorts D and E, respectively. f, Repeated TB40/E (top panels representative of measurements in four independent BLT-L mice) and AD169 (bottom panels representative of measurements in four independent BLT-L mice) exposure induced high frequencies of HCMV-specific CD8⁺ T cells as determined by pentamer reactivity. Full details of immune reactivity for each multiple exposed BLT-L mouse are indicated in Supplementary Tables 7 and 8.