TY - JOUR
T1 - Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators
AU - Sørensen, Rikke Baek
AU - Hadrup, Sine Reker
AU - Svane, Inge Marie
AU - Hjortsø, Mads Christian
AU - Thor Straten, Per
AU - Andersen, Mads Hald
AU - Hjortsø, Mads Christian
AU - Andersen, Mads Hald
PY - 2011/2/17
Y1 - 2011/2/17
N2 - Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in normal and pathologic settings. Here, we describe that spontaneous cytotoxic T-cell reactivity against IDO exists not only in patients with cancer but also in healthy persons. We show that the presence of such IDO-specific CD8+ T cells boosted T-cell immunity against viral or tumor-associated antigens by eliminating IDO + suppressive cells. This had profound effects on the balance between interleukin-17 (IL-17)-producing CD4+ T cells and regulatory T cells. Furthermore, this caused an increase in the production of the proinflammatory cytokines IL-6 and tumor necrosis factor-α while decreasing the IL-10 production. Finally, the addition of IDO-inducing agents (ie, the TLR9 ligand cytosinephosphate-guanosine, soluble cytotoxic T lymphocyte-associated antigen 4, or interferon γ) induced IDO-specific T cells among peripheral blood mononuclear cells from patients with cancer as well as healthy donors. In the clinical setting, IDO may serve as an important and widely applicable target for immunotherapeutic strategies in which IDO plays a significant regulatory role. We describe for the first time effector T cells with a general regulatory function that may play a vital role for the mounting or maintaining of an effective adaptive immune response. We suggest terming such effector T cells "supporter T cells."
AB - Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in normal and pathologic settings. Here, we describe that spontaneous cytotoxic T-cell reactivity against IDO exists not only in patients with cancer but also in healthy persons. We show that the presence of such IDO-specific CD8+ T cells boosted T-cell immunity against viral or tumor-associated antigens by eliminating IDO + suppressive cells. This had profound effects on the balance between interleukin-17 (IL-17)-producing CD4+ T cells and regulatory T cells. Furthermore, this caused an increase in the production of the proinflammatory cytokines IL-6 and tumor necrosis factor-α while decreasing the IL-10 production. Finally, the addition of IDO-inducing agents (ie, the TLR9 ligand cytosinephosphate-guanosine, soluble cytotoxic T lymphocyte-associated antigen 4, or interferon γ) induced IDO-specific T cells among peripheral blood mononuclear cells from patients with cancer as well as healthy donors. In the clinical setting, IDO may serve as an important and widely applicable target for immunotherapeutic strategies in which IDO plays a significant regulatory role. We describe for the first time effector T cells with a general regulatory function that may play a vital role for the mounting or maintaining of an effective adaptive immune response. We suggest terming such effector T cells "supporter T cells."
U2 - 10.1182/blood-2010-06-288498
DO - 10.1182/blood-2010-06-288498
M3 - Journal article
C2 - 21079151
SN - 0006-4971
VL - 117
SP - 2200
EP - 2210
JO - Blood
JF - Blood
IS - 7
ER -
