Alterations in cell signaling and related effector functions in T lymphocytes in burn/trauma/septic injuries.
Suppressions in T-cell responses in burn, trauma, and septic injuries could result from alterations in the T-cell signaling pathway linked to the stimulation of the T-cell antigen receptor complex. Recent studies have correlated T-cell IL-2 expression and proliferation with those in the signaling pathways. T-cells from injured hosts were stimulated with a calcium ionophore (to upregulate Ca2+ mobilization) and a phorbol ester (to activate protein kinase C); these T-cells were found to be unresponsive. These studies suggested that the defect in the pathway is located downstream of the Ca2+ mobilization and protein kinase C activation steps. In contrast, the exposure of T-cells from injured hosts to a phorbol ester along with a mitogen (PHA) was found to abrogate the burn/trauma injury-induced suppression in IL-2 expression; these studies remain to be clarified further. Studies from the author's laboratory have shown decreased Ca2+ mobilization and tyrosine phosphorylation correlated with suppressed T-cell IL-2 production and proliferation. These studies support the view that the T-cell signaling defect in the injury condition occurs at the Ca2+ signal step and/or in the upstream signaling component effecting protein tyrosine phosphorylation.
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D002056:Burns / Q000097:blood*; D002450:Cell Communication / Q000502:physiology*; D002455:Cell Division / Q000235:genetics; D006801:Humans; D018805:Sepsis / Q000097:blood*; D015398:Signal Transduction / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*; D014158:Transcription, Genetic; D014947:Wounds and Injuries / Q000097:blood*