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Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition) ›› 2023, Vol. 17 ›› Issue (01): 32-40. doi: 10.3877/cma.j.issn.1674-1358.2023.01.006

• Research Article • Previous Articles     Next Articles

Dynamic recovery of splenic T lymphocytes function in mice with endotoxin-induced sepsis

Yang Fan1, Guoli Li1, Yu Hao1, Yu Cao1, Fangyuan Li1, Zengtao Wang1, Hui Zeng1,()   

  1. 1. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
  • Received:2022-02-18 Online:2023-02-15 Published:2023-04-26
  • Contact: Hui Zeng

Abstract:

Objective

To investigate the dynamic recovery process of splenic T lymphocyte function and their subsets in mice after lipopolysaccharide (LPS) administration.

Methods

High dose LPS (10 mg/kg, once) was administered intraperitoneally to establish septic mouse model. On day 0, day 7, day 14, and day 28 after LPS treatment, flow cytometry was used to check the proportions of naive T cells, effector memory T cells, and central memory T cells in splenic CD4+ and CD8+ T cells. The expression of cell surface activation molecules (CD38, CD69) and co-inhibitory molecules (PD-1, TIGIT), as well as the ability of splenic CD4+ T cells to secrete cytokines IL-2, IFN-γ and CD8+ T cells to release granzyme B. Normal distribution data used one-way ANOVA test for variance analysis and used holm-Sidak’s test for multiple comparison. Skewness distribution data used Kruskal-wallis test for variance analysis and used Bonferroni method for multiple comparison.

Results

On day 7 after LPS challenge, compared with the baseline, the proportions of splenic naive CD4+ and CD8+ T cells in mice were significantly decreased (F = 52.22, P < 0.0001; F = 10.87, P = 0.0019); the proportions of effector memory CD4+ and CD8+ T cells were significantly increased (F = 20.54, P < 0.0001; F = 26.03, P < 0.0001); the proportions of CD4+CD38+ (F = 35.40, P < 0.0001), CD4+CD69+ (F = 45.65, P < 0.0001), CD4+PD-1+ (F = 20.55, P < 0.0001), CD4+TIGIT+ (F = 19.20, P < 0.0001), CD8+CD38+ (F = 56.76, P < 0.0001), CD8+CD69+ (F = 59.47, P < 0.0001), CD8+PD-1+ (F = 11.15, P = 0.0013) and CD8+TIGIT+ (F = 21.21, P < 0.0001) cells were significantly increased. These indicators gradually recovered compared with the baseline within 14 days. On day 28 after LPS challenge, the proportions of naive CD4+ T cells (F = 52.22, P < 0.0001), effector memory CD4+ T cells (F = 20.54, P = 0.0093), CD4+CD69+ (F = 45.65, P = 0.0037), CD4+PD-1+ (F = 20.55, P = 0.0255) and CD4+TIGIT+ (F = 19.20, P = 0.0087) cells were not returned to the baseline level; the proportion of CD8+IFN-γ+ T cells (F = 14.33, P < 0.0001) was still higher than the baseline.

Conclusions

After LPS challenge, differences exist during the recovery process of splenic CD4+ T and CD8+ T cells in mice within 28 days. The overall recovery process of splenic CD4+ T cells function in septic mice was slower than that of CD8+ T cells after LPS treatment.

Key words: Sepsis, Spleen, Lymphocytes, Activation, Co-inhibitory molecules

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