Fig. 1
Chemokine receptor inhibitor vMIP-II promotes the conversion of effector CD8+ T into TCM cells in the reconstitution of cellular immunity in patients with COVID-19. a Reduction of lesions of lung CT treated by vMIP-II. Five common patients with SARS-CoV-2 virus were scanned by lung CT before and 1 week after vMIP-II treatment. The ground glass lesions and white areas of the lungs were significantly alleviated after 1-week treatment. b Cytokine level of different groups of PBMCs stimulated by S protein in convalescent patients after 1 week of being negative. Different groups of separated PBMCs were added with S protein (100 ng/mL S1 + S2, w/w = 2:1) and detected by cytokine kits, *p value < 0.05. c Proliferation of PMBCs stimulated by S protein in convalescent groups after 1 week of being negative. Compared with the common symptomatic group, vMIP-II group and non-symptomatic group, *p-value < 0.05 (n = 5). d Flow cytometry detection of memory CD8+ T cells. Different subgroups of memory CD8+ T cells were distinguished by CD45RA and CD62L. The third line was the detection of inhibitory molecules on the surface of CD8+ T cells. The depleted CD8+ T cells (TEX) were distinguished by the highly expressed inhibitory molecules PD-1 and Tim-3. e Proportion and distribution of CD8+ T-cell subgroups in different vMIP-II to S protein. Compared with control group, * p value <0.05. (n = 3). f MA map of differentially expressed genes. Gene differential expression analysis on effector CD8+ T cells sample of vMIP-II treament group and S protein group was performed by DESeq. g Western blotting detected that vMIP-II reduced the G protein expression of CD8+ T cells. In the presence of Gi α antisense oligodeoxynucleotides, the reduction of G protein induced by vMIP-II is more obvious. h Compared with the control group, vMIP-II, significantly inhibited the rapid influx of calcium, and the p value of the S protein and vMIP-II groups was <0.01. i, j The effect of vMIP-II on the phosphorylation of PK, LDH, Dnmt3a, PI3K, and Akt. Under S protein stimulation, CD8+ T cells were incubated with vMIP-II or without vMIP-II. The results showed that in the presence of vMIP-II, the phosphorylation level was significantly reduced. k, l. vMIP-II reduced the mitochondrial membrane potential of CD8+ T cells. The left side is the vMIP-II treatment group, and the right side is the control group. Compared with the control group, the intensity of the fluorescent color was reduced, and the *p value was <0.01. m, n. The effect of vMIP-II, on mitochondrial proliferation genes SIRT1, PGC-1ɑ, and autophagy genes LC3, PINK1, Parkin genes. Under S protein stimulation, CD8+ T cells were incubated with vMIP-II or without vMIP-II . The results showed that in the presence of vMIP-II, mitochondrial proliferation-related genes were suppressed and autophagy-related genes increased. o The effect of vMIP-II on mitochondrial network structure. The left side is the S protein control group, and the right side is the vMIP-II treatment group. It can be seen that fragmented mitochondria appeared after vMIP-II treatment, and the mitochondrial network was destroyed, 400×, *p value < 0.01. p The effect of vMIP-II on downstream proteins of mTOR pathway. Under S protein stimulation, the S protein CD8+ T cells were incubated with vMIP-II for 6 h or 12 h. The results showed that in the presence of vMIP-II, the downstream proteins of the mTOR pathway were inhibited at 6 h, and the inhibition was more obvious at 12 h
