Fig. 4
sCD4 downregulated TLR4 inflammation through MHC II in macrophages. a, b TNF/IL-6 measurement as in Fig. 1I except that MHC II-/- BMDM were co-cultured with (a) an equal number of CD4+ T cells, or (b) 25 nM sCD4 protein. c Survival rates and (d) serum TNF/IL-6 24 h after LPS i.p. injection in wt littermates or MHC II−/− mice pre-treated with a single dose of sCD4 (10 mg/kg). TNF/IL-6 in supernatants after (e) MHC II−/− BMDM were pre-treated with 25 nM sCD40L, or (f) CD40−/− BMDM cells with 25 nM sCD4 before LPS stimulation. Survival rates and serum TNF/IL-6 in mice with (g–h) macrophages ablated (ΔMΦ) or (i–j) ΔMΦ mice reconstituted with either MHCII+/+ or MHCII−/− macrophages, that received 10 mg/kg sCD4 or PBS before i.p. LPS stimulation. k TNF/IL-6 in the supernatants 12 h after peritoneal macrophages that transiently overexpressed with the indicated MHCII subunits or cytoplasmic tail-truncational mutants (ΔCT) were stimulated with LPS or LPS plus 25 nM sCD4. Mean ± SD are shown; n = 3–10 mice used where indicated; Statistics (ns, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001): Log-rank (Mantel-Cox) test (c, g, i (left), j (left)), Unpaired t test (a–b, d, e–f, h, i (right), j (right), k)
