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The injury progression of T lymphocytes in a mouse model with subcutaneous injection of a high dose of sulfur mustard

TitleThe injury progression of T lymphocytes in a mouse model with subcutaneous injection of a high dose of sulfur mustard
Publication TypeJournal Article
Year of Publication2014
AuthorsMei Y.Z, Zhang X.R, Jiang N., Cheng J.P, Liu F., Zheng P., Zhou W.X, Zhang Y.X
JournalMil Med ResMil Med ResMil Med Res
Volume1
Pagination28
ISBN Number2095-7467 (Print)<br/>2054-9369 (Linking)
Accession Number25722879
Abstract

BACKGROUND: In clinical studies, the findings on sulfur mustard (SM) toxicity for CD3(+)CD4(+) and CD3(+)CD8(+) T lymphocyte subsets are contradictory. In animal experiments, the effect of SM on the T cell number and proliferation is incompatible and is even the opposite of the results in human studies. In this study, we observed the dynamic changes of T lymphocytes in the first week in a high-dose SM-induced model. METHODS: Mice were exposed to SM by subcutaneous injection (20 mg/kg) and were sacrificed 4 h, 24 h, 72 h and 168 h later. Spleen T lymphocyte proliferation was evaluated by (3)H-TdR. Flow cytometric analysis was used to observe the percentage of CD3(+)CD4(+) and CD3(+)CD8(+) T lymphocyte subsets. The IL-1beta, IL-6, IL-10 and TNF-alpha levels in plasma were assayed using the Luminex method. DNA damage in bone marrow cells was observed with the single cell gel electrophoresis technique (SCGE). RESULTS: SM continuously inhibited the proliferation of lymphocytes for 7 days, and there was a significant rebound of Con A-induced T lymphocyte proliferation only at 24 h. The percentage of CD3(+)CD4(+) and CD3(+)CD8(+) lymphocytes was upregulated, which was accompanied by increased IL-1beta and TNF-alpha and decreased IL-10. The IL-6 level was gradually decreased in the PG group at 4 h. The peak of lymphocytic apoptosis and DNA damage occurred at 24 h and 72 h, respectively. CONCLUSION: Our results show that SM significantly inhibited T lymphocyte proliferation as well as induced CD3(+)CD4(+) and CD3(+)CD8(+) upregulation. SM intoxication also significantly increased the levels of pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and inhibited the level of anti-inflammatory cytokine IL-10. Our results may partly be due to the significant SM induced significant apoptosis and necrosis of lymphocytes as well as DNA damage of bone marrow cells. The results provided a favorable evaluation of SM immune toxicity in an animal model.

Short TitleMilitary Medical ResearchMilitary Medical Research
Alternate JournalMilitary Medical Research

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