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- Thomas Murphy, Hugh Paterson, Selwyn Rogers, John A Mannick, and James A Lederer.
- Department of Surgery, Julian and Eunice Cohen Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
- Ann. Surg. 2003 Sep 1; 238 (3): 401411401-10; discussion 410-1.
ObjectiveTo determine the percentages of major T lymphocyte subsets in the circulating peripheral blood mononuclear cell population in patients with major traumatic injury at early and late time points and to determine the expression of coreceptors and cytokine production by these T cell subsets.Summary Background DataPrior studies suggest that serious injury in humans suppresses the adaptive immune system as revealed by diminished proliferation and altered cytokine production in response to polyclonal T cell activation. However, the contribution of individual cell types to this immune dysfunction has not been well characterized.MethodsThe percentage of circulating CD4+ and CD8+ T cells and the relative density of CD4 and CD8 coreceptor expression was determined by flow cytometry in 17 consecutive trauma patients (injury severity score > 20) within 24 hours of injury and at day 7. Intracellular expression of the cytokines interleukin 2 (IL-2), interferon gamma (IFNgamma), IL-4, and IL-10 were also studied after stimulation with bacterial superantigen (SEB). Patients were compared with age- and sex-matched controls and to themselves for differences between early and late cytokine expression.ResultsThe percentage of circulating CD4+ and CD8+ T cells was decreased versus controls at day 1 and further decreased by day 7 following injury. CD4 and CD8 cell surface expression was also decreased at days 1 and 7. CD4+ T cells in injured patients responded to SEB activation with decreased expression of IFNgamma and IL-2 on day 1 versus controls (P < 0.05) and of all 4 cytokines by day 7 (P < 0.05), while CD8+ T cells showed diminished expression of IFNgamma and IL-2 only at both time points. When day 1 and day 7 cytokine expression results were compared in the same patients, CD4+ T cells showed diminished expression of IFNgamma, IL-2, and IL-4 by day 7 (P < 0.05), but maintained expression of IL-10. CD8 T cells showed diminished expression of IFNgamma only.ConclusionsSevere injury induces a loss of circulating CD4+ and CD8+ T lymphocytes and diminished coreceptor expression by these cells. Both T cell subsets show progressive loss of immunostimulatory cytokine production with maintenance of potentially suppressive IL-10 production. These events may have negative consequences for host defense.
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