Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity

Malcolm P. MacConmara, Adrian A. Maung, Satoshi Fujimi, Ann M. McKenna, Adam Delisle, Peter H. Lapchak, Selwyn Rogers, James A. Lederer, John A. Mannick

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

OBJECTIVES: We recently reported increased CD4 CD25 T regulatory (Treg) activity after burn injury in mice. This study sought to determine if Tregs mediate the reduction in TH1-type immunity after serious injury in man and if Treg function is altered by injury. METHODS: Peripheral blood was withdrawn from 19 consenting adult patients (35.1 ± 16.3 years of age) with Injury Severity Scores (ISS) 36.6 ± 13.9 on days 1 and 7 after trauma and from 5 healthy individuals. CD4 T cells were purified and sorted into Treg (CD25) and Treg-depleted populations. After activation of cells with anti-CD3/CD28 antibody, production of the TH1-type cytokine IFNγ, TH2-type cytokines (IL-4 and IL-5), and the inhibitory cytokine IL-10 was measured using cytometric bead arrays. Treg activity was measured by in vitro suppression of autologous CD4 T cell proliferation. RESULTS: All patients survived, 9 (47%) developed infection postinjury. IFNγ production by patient CD4 T cells was decreased on day 1 and day 7, when compared with healthy controls. However, when Tregs were depleted from the CD4 T cells, the IFNγ production increased to control levels. Tregs were the chief source of IL-4 and IL-5 as well as IL-10. Treg suppression of T cell proliferation increased significantly from day 1 to day 7 after injury. CONCLUSIONS: We demonstrate for the first time that human Tregs are increased in potency after severe injury. Most significantly, Tregs are important mediators of the suppression of T cell activation and the reduction in TH1 cytokine production found after injury.

Original languageEnglish (US)
Pages (from-to)514-521
Number of pages8
JournalAnnals of Surgery
Volume244
Issue number4
DOIs
StatePublished - Oct 2006

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Regulatory T-Lymphocytes
Immunity
Wounds and Injuries
T-Lymphocytes
Cytokines
Interleukin-5
Interleukin-4
Interleukin-10
Cell Proliferation
Injury Severity Score
Antibody Formation
Infection
Population

ASJC Scopus subject areas

  • Surgery

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Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity. / MacConmara, Malcolm P.; Maung, Adrian A.; Fujimi, Satoshi; McKenna, Ann M.; Delisle, Adam; Lapchak, Peter H.; Rogers, Selwyn; Lederer, James A.; Mannick, John A.

In: Annals of Surgery, Vol. 244, No. 4, 10.2006, p. 514-521.

Research output: Contribution to journalArticle

MacConmara, MP, Maung, AA, Fujimi, S, McKenna, AM, Delisle, A, Lapchak, PH, Rogers, S, Lederer, JA & Mannick, JA 2006, 'Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity', Annals of Surgery, vol. 244, no. 4, pp. 514-521. https://doi.org/10.1097/01.sla.0000239031.06906.1f
MacConmara, Malcolm P. ; Maung, Adrian A. ; Fujimi, Satoshi ; McKenna, Ann M. ; Delisle, Adam ; Lapchak, Peter H. ; Rogers, Selwyn ; Lederer, James A. ; Mannick, John A. / Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity. In: Annals of Surgery. 2006 ; Vol. 244, No. 4. pp. 514-521.
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AU - MacConmara, Malcolm P.

AU - Maung, Adrian A.

AU - Fujimi, Satoshi

AU - McKenna, Ann M.

AU - Delisle, Adam

AU - Lapchak, Peter H.

AU - Rogers, Selwyn

AU - Lederer, James A.

AU - Mannick, John A.

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N2 - OBJECTIVES: We recently reported increased CD4 CD25 T regulatory (Treg) activity after burn injury in mice. This study sought to determine if Tregs mediate the reduction in TH1-type immunity after serious injury in man and if Treg function is altered by injury. METHODS: Peripheral blood was withdrawn from 19 consenting adult patients (35.1 ± 16.3 years of age) with Injury Severity Scores (ISS) 36.6 ± 13.9 on days 1 and 7 after trauma and from 5 healthy individuals. CD4 T cells were purified and sorted into Treg (CD25) and Treg-depleted populations. After activation of cells with anti-CD3/CD28 antibody, production of the TH1-type cytokine IFNγ, TH2-type cytokines (IL-4 and IL-5), and the inhibitory cytokine IL-10 was measured using cytometric bead arrays. Treg activity was measured by in vitro suppression of autologous CD4 T cell proliferation. RESULTS: All patients survived, 9 (47%) developed infection postinjury. IFNγ production by patient CD4 T cells was decreased on day 1 and day 7, when compared with healthy controls. However, when Tregs were depleted from the CD4 T cells, the IFNγ production increased to control levels. Tregs were the chief source of IL-4 and IL-5 as well as IL-10. Treg suppression of T cell proliferation increased significantly from day 1 to day 7 after injury. CONCLUSIONS: We demonstrate for the first time that human Tregs are increased in potency after severe injury. Most significantly, Tregs are important mediators of the suppression of T cell activation and the reduction in TH1 cytokine production found after injury.

AB - OBJECTIVES: We recently reported increased CD4 CD25 T regulatory (Treg) activity after burn injury in mice. This study sought to determine if Tregs mediate the reduction in TH1-type immunity after serious injury in man and if Treg function is altered by injury. METHODS: Peripheral blood was withdrawn from 19 consenting adult patients (35.1 ± 16.3 years of age) with Injury Severity Scores (ISS) 36.6 ± 13.9 on days 1 and 7 after trauma and from 5 healthy individuals. CD4 T cells were purified and sorted into Treg (CD25) and Treg-depleted populations. After activation of cells with anti-CD3/CD28 antibody, production of the TH1-type cytokine IFNγ, TH2-type cytokines (IL-4 and IL-5), and the inhibitory cytokine IL-10 was measured using cytometric bead arrays. Treg activity was measured by in vitro suppression of autologous CD4 T cell proliferation. RESULTS: All patients survived, 9 (47%) developed infection postinjury. IFNγ production by patient CD4 T cells was decreased on day 1 and day 7, when compared with healthy controls. However, when Tregs were depleted from the CD4 T cells, the IFNγ production increased to control levels. Tregs were the chief source of IL-4 and IL-5 as well as IL-10. Treg suppression of T cell proliferation increased significantly from day 1 to day 7 after injury. CONCLUSIONS: We demonstrate for the first time that human Tregs are increased in potency after severe injury. Most significantly, Tregs are important mediators of the suppression of T cell activation and the reduction in TH1 cytokine production found after injury.

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