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

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 METHODS:Peripheral blood was withdrawn from 19 consenting adult patients (35.1 +/- 16.3 years of age) with Injury Severity Scores (ISS) 36.6 +/- 13.9 on days 1 and 7 after trauma and from 5 healthy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(high)) and Treg-depleted populations. After activation of cells with anti-CD3/CD28 antibody, production of the TH1-type cytokine IFNgamma, 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. IFNgamma 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 IFNgamma 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.

journal_name

Ann Surg

journal_title

Annals of surgery

authors

MacConmara MP,Maung AA,Fujimi S,McKenna AM,Delisle A,Lapchak PH,Rogers S,Lederer JA,Mannick JA

doi

10.1097/01.sla.0000239031.06906.1f

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

514-23

issue

4

eissn

0003-4932

issn

1528-1140

pii

00000658-200610000-00006

journal_volume

244

pub_type

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