Use of Intracellular Cytokine Staining and Bacterial Superantigen to Document Suppression of the Adaptive Immune System in Injured Patients

Thomas Murphy, Hugh Paterson, Selwyn Rogers, John A. Mannick, James A. Lederer, Basil A. Pruitt, Anthony A. Meyer, Charles E. Lucas

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objective: To 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 Data: Prior 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. Methods: The 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 (IFNγ), 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. Results. The 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 IFNγ 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 IFNγ 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 IFNγ, IL-2, and IL-4 by day 7 (P < 0.05), but maintained expression of IL-10. CD8 T cells showed diminished expression of IFNγ only. Conclusions: Severe 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.

Original languageEnglish (US)
Pages (from-to)401-411
Number of pages11
JournalAnnals of Surgery
Volume238
Issue number3
StatePublished - Sep 2003
Externally publishedYes

Fingerprint

Superantigens
Immune System
Staining and Labeling
Cytokines
T-Lymphocytes
Interferon-gamma
Interleukin-2
Wounds and Injuries
T-Lymphocyte Subsets
Interleukin-10
Interleukin-4
Specific Gravity
Injury Severity Score
Blood Cells
Flow Cytometry
Cell Count
Maintenance

ASJC Scopus subject areas

  • Surgery

Cite this

Murphy, T., Paterson, H., Rogers, S., Mannick, J. A., Lederer, J. A., Pruitt, B. A., ... Lucas, C. E. (2003). Use of Intracellular Cytokine Staining and Bacterial Superantigen to Document Suppression of the Adaptive Immune System in Injured Patients. Annals of Surgery, 238(3), 401-411.

Use of Intracellular Cytokine Staining and Bacterial Superantigen to Document Suppression of the Adaptive Immune System in Injured Patients. / Murphy, Thomas; Paterson, Hugh; Rogers, Selwyn; Mannick, John A.; Lederer, James A.; Pruitt, Basil A.; Meyer, Anthony A.; Lucas, Charles E.

In: Annals of Surgery, Vol. 238, No. 3, 09.2003, p. 401-411.

Research output: Contribution to journalArticle

Murphy, T, Paterson, H, Rogers, S, Mannick, JA, Lederer, JA, Pruitt, BA, Meyer, AA & Lucas, CE 2003, 'Use of Intracellular Cytokine Staining and Bacterial Superantigen to Document Suppression of the Adaptive Immune System in Injured Patients', Annals of Surgery, vol. 238, no. 3, pp. 401-411.
Murphy, Thomas ; Paterson, Hugh ; Rogers, Selwyn ; Mannick, John A. ; Lederer, James A. ; Pruitt, Basil A. ; Meyer, Anthony A. ; Lucas, Charles E. / Use of Intracellular Cytokine Staining and Bacterial Superantigen to Document Suppression of the Adaptive Immune System in Injured Patients. In: Annals of Surgery. 2003 ; Vol. 238, No. 3. pp. 401-411.
@article{5dfbec345b0b48deaa20f670c568d99a,
title = "Use of Intracellular Cytokine Staining and Bacterial Superantigen to Document Suppression of the Adaptive Immune System in Injured Patients",
abstract = "Objective: To 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 Data: Prior 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. Methods: The 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 (IFNγ), 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. Results. The 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 IFNγ 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 IFNγ 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 IFNγ, IL-2, and IL-4 by day 7 (P < 0.05), but maintained expression of IL-10. CD8 T cells showed diminished expression of IFNγ only. Conclusions: Severe 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.",
author = "Thomas Murphy and Hugh Paterson and Selwyn Rogers and Mannick, {John A.} and Lederer, {James A.} and Pruitt, {Basil A.} and Meyer, {Anthony A.} and Lucas, {Charles E.}",
year = "2003",
month = "9",
language = "English (US)",
volume = "238",
pages = "401--411",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Use of Intracellular Cytokine Staining and Bacterial Superantigen to Document Suppression of the Adaptive Immune System in Injured Patients

AU - Murphy, Thomas

AU - Paterson, Hugh

AU - Rogers, Selwyn

AU - Mannick, John A.

AU - Lederer, James A.

AU - Pruitt, Basil A.

AU - Meyer, Anthony A.

AU - Lucas, Charles E.

PY - 2003/9

Y1 - 2003/9

N2 - Objective: To 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 Data: Prior 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. Methods: The 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 (IFNγ), 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. Results. The 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 IFNγ 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 IFNγ 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 IFNγ, IL-2, and IL-4 by day 7 (P < 0.05), but maintained expression of IL-10. CD8 T cells showed diminished expression of IFNγ only. Conclusions: Severe 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.

AB - Objective: To 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 Data: Prior 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. Methods: The 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 (IFNγ), 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. Results. The 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 IFNγ 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 IFNγ 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 IFNγ, IL-2, and IL-4 by day 7 (P < 0.05), but maintained expression of IL-10. CD8 T cells showed diminished expression of IFNγ only. Conclusions: Severe 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.

UR - http://www.scopus.com/inward/record.url?scp=0141871978&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141871978&partnerID=8YFLogxK

M3 - Article

C2 - 14501506

AN - SCOPUS:0141871978

VL - 238

SP - 401

EP - 411

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 3

ER -