Fig. 1
Membrane bound CD4 in T cells controlled TLR4 inflammation. a Survival rates, (b) CD4+ T cell counts in the indicated organs, and (d) serum TNF and IL-6 were measured 12 h after i.p. LPS (n = 7–8). c Survival rates were measured after CLP (n = 7–16). e Absolute numbers of peripheral CD4+ T cells, (f) indicated cytokines of BALF were measured in COVID-19 patients (n = 15). Survival rates and TNF/IL-6 levels were measured as in (a–c) except that CD4+ T cells were (g) pre-depleted (GK1.5) for 2 days, or (h) supplemented to nude mice for 7 days, before LPS injection. i–k hACE2 mice pre-treated with GK1.5 antibody or isotype IgG were infected with SARS-CoV-2 for 7days. i Fold changes of TNF and IL-6 mRNA normalized to actin in the lung by qPCR and (j–k) representative sections and pathology score of the lobe of left lung (with respective magnifications of areas of interest) on day 7. SARS-CoV-2 virus (pfu 1 × 102 in box; pfu 1 × 105 in circle). l, m Measurement of TNF and IL-6 in supernatants of BMDM 16 h after incubation with LPS (100 ng/mL), in the absence or presence of (l) T cells of the indicated origins (macrophages: T cells = 1:1), or (m) naive CD4+ T cells with the indicated blocking mAb against CD4 (RM4-5; GK1.5). n TNF and IL-6 in supernatants 3 h after LPS treatment of THP-1 cells co-cultured with HeLa or TZM-B1 cells. Mean ± SD are shown; n = 3–11 mice used where indicated; Statistics (ns, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001): Log-rank (Mantel-Cox) test (a, c, g (left), h (left)), Unpaired t test (b, d–f, g (right), h (right), i, k), one-way ANOVA with Dunnett’s analysis (l, m, n)
