Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity.
OBJECTIVE
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Peripheral blood was withdrawn from 19 consenting adult patients (35.1 +/- 16.3 years of age) with Injury Severity Scores (ISS) 36.6 +/- 13.9 on days 1 and 7 after trauma and from 5 healthy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.
MacConmara
Malcolm P
MP
Department of Surgery (Immunology), Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Maung
Adrian A
AA
Fujimi
Satoshi
S
McKenna
Ann M
AM
Delisle
Adam
A
Lapchak
Peter H
PH
Rogers
Selwyn
S
Lederer
James A
JA
Mannick
John A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D014947:Wounds and Injuries / Q000097:blood / Q000276:immunology*
D015375:Receptors, Interleukin-2