| Abstract
| - A considerable amount of research has focused on elucidating the mechanisms by which cytokines synthesized by cells of the innate immune system participate in the life-threatening multiple-organ failure of endotoxic shock. We show here that αβ T cells, which are archetypes of the adaptive cellular immune response, suppress the proinflammatory cascade triggered during the early stages of lipopolysaccharide (LPS)-induced endotoxemia. The absence of αβ T cells led to the fulminant death of LPS-challenged mice, coinciding with a massive release of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ and a marked reduction in the synthesis of the immunosuppressive cytokine transforming growth factor (TGF)-β. Cytotoxic T lymphocyte antigen (CTLA)-positive αβ T cells emerging shortly after LPS challenge appear to control TGF-β synthesis. The neutralization of either TGF-β or CTLA4 resulted in similar increases in IFN-γ and TNF-α serum concentrations in LPS-challenged mice. These observations suggest that suppressor αβ T lymphocytes protect against the proinflammatory cascade unleashed during the innate stages of endotoxemia
|
