Suppressor alphabeta T lymphocytes control innate resistance to endotoxic shock.
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 alphabeta 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 alphabeta T cells led to the fulminant death of LPS-challenged mice, coinciding with a massive release of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma and a marked reduction in the synthesis of the immunosuppressive cytokine transforming growth factor (TGF)-beta. Cytotoxic T lymphocyte antigen (CTLA)-positive alphabeta T cells emerging shortly after LPS challenge appear to control TGF-beta synthesis. The neutralization of either TGF-beta or CTLA4 resulted in similar increases in IFN-gamma and TNF-alpha serum concentrations in LPS-challenged mice. These observations suggest that suppressor alphabeta T lymphocytes protect against the proinflammatory cascade unleashed during the innate stages of endotoxemia.
Jones-Carson
Jessica
J
Departments of Medicine, and Microbiology, University of Colorado Health Sciences Center, Denver, USA.
Fantuzzi
Giamila
G
Siegmund
Britta
B
Dinarello
Charles
C
Tracey
Kevin J
KJ
Wang
Haichao
H
Fang
Ferric C
FC
Vazquez-Torres
Andres
A
D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000276:immunology*; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology*; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D008070:Lipopolysaccharides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha