Noble, Alistair;
Leggat, Jamie A.;
Inderberg, Else M.
CD8+ immunoregulatory cells in the graft‐versus‐host reaction: CD8 T cells activate dendritic cells to secrete interleukin‐12/interleukin‐18 and induce T helper 1 autoantibody
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Medientyp:
E-Artikel
Titel:
CD8+ immunoregulatory cells in the graft‐versus‐host reaction: CD8 T cells activate dendritic cells to secrete interleukin‐12/interleukin‐18 and induce T helper 1 autoantibody
Beteiligte:
Noble, Alistair;
Leggat, Jamie A.;
Inderberg, Else M.
Beschreibung:
<jats:title>Summary</jats:title><jats:p>Initiation of cell‐mediated immunity or autoimmunity requires secretion of interleukin (IL)‐12 from dendritic cells (DC), which drives the generation of T helper 1 (Th1) effector cells in synergy with IL‐18. Induction of IL‐12 can be triggered by microbial stimuli but also requires signals from activated T cells. We investigated interactions between alloreactive CD4 and CD8 T cells in mixed lymphocyte reactions (MLR) <jats:italic>in vitro</jats:italic> and in the graft‐versus‐host reaction (GVHR) <jats:italic>in vivo</jats:italic>. In a parent‐into‐F1 model of GVHR, donor CD8 cells were found to suppress the hyper‐immunoglobulin E (IgE) syndrome, anti‐DNA immunoglobulin G1 (IgG1) autoantibodies and donor CD4‐cell expansion, but were essential for Th1‐dependent immunoglobulin G2a (IgG2a) autoantibody production and release of serum IL‐12 p40. <jats:italic>In vitro</jats:italic>, addition of alloreactive CD8 cells to CD4 cells and mature DC enhanced Th1 development. CD4 and CD8 T cells induced IL‐18 from DC and primed for IL‐12 p70 secretion via interferon‐γ (IFN‐γ) or tumour necrosis factor‐α (TNF‐α). However CD8 T cells, but not CD4 cells, released IFN‐γ/TNF‐α after primary stimulation. The data suggest that rapid release of inflammatory cytokines from central memory‐type CD8 cells early in immunity is critical for induction of Th1 cells via DC activation and IL‐12 production. This pathway could provide a means for amplification of cell‐mediated autoimmunity in the absence of microbial stimuli.</jats:p>