Enhanced regulatory T cell activity is an element of the host response to injury.
CD4+CD25+ regulatory T cells (Tregs) play a critical role in suppressing the development of autoimmune disease, in controlling potentially harmful inflammatory responses, and in maintaining immune homeostasis. Because severe injury triggers both excessive inflammation and suppressed adaptive immunity, we wished to test whether injury could influence Treg activity. Using a mouse burn injury model, we demonstrate that injury significantly enhances Treg function. This increase in Treg activity is apparent at 7 days after injury and is restricted to lymph node CD4+CD25+ T cells draining the injury site. Moreover, we show that this injury-induced increase in Treg activity is cell-contact dependent and is mediated in part by increased cell surface TGF-beta1 expression. To test the in vivo significance of these findings, mice were depleted of CD4+CD25+ T cells before sham or burn injury and then were immunized to follow the development of T cell-dependent Ag-specific immune reactivity. We observed that injured mice, which normally demonstrate suppressed Th1-type immunity, showed normal Th1 responses when depleted of CD4+CD25+ T cells. Taken together, these observations suggest that injury can induce or amplify CD4+CD25+ Treg function and that CD4+CD25+ T cells contribute to the development of postinjury immune suppression.
Ni Choileain
Niamh
N
Department of Surgery (Immunology), Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02115, USA.
MacConmara
Malcolm
M
Zang
Yan
Y
Murphy
Thomas J
TJ
Mannick
John A
JA
Lederer
James A
JA
D000818:Animals; D002056:Burns / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D015704:CD4 Antigens; D016207:Cytokines; D015375:Receptors, Interleukin-2; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1