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

Abstract

BackgroundIn 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.MethodsMice 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 3H-TdR. Flow cytometric analysis was used to observe the percentage of CD3+CD4+ and CD3+CD8+ T lymphocyte subsets. The IL-1β, IL-6, IL-10 and TNF-α 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).ResultsSM 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-1β and TNF-α 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.ConclusionOur 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-1β, IL-6 and TNF-α) 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.

Emerging targets for treating sulfur mustard–induced injuries

“…Activation of T cell–mediated responses has also been reported in animal models of SM inhalation . However, in one model, SM caused decreased T cell proliferation . The importance of inflammatory cells in CEES‐induced injuries is further supported by a study that showed protection in rats following neutrophil depletion .…”

“…20 However, in one model, SM caused decreased T cell proliferation. 73 The importance of inflammatory cells in CEES-induced injuries is further supported by a study that showed protection in rats following neutrophil depletion. 74 While these studies underscore the critical role of neutrophils in contributing to the inflammatory phenotype, severe exposures lead to neutropenia, resulting in increased susceptibility to infections and increased mortality.…”