Article: article from journal or magazin.
Distinct effects of IL-18 on the engraftment and function of human effector CD8 T cells and regulatory T cells.
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
IL-18 has pleotropic effects on the activation of T cells during antigen presentation. We investigated the effects of human IL-18 on the engraftment and function of human T cell subsets in xenograft mouse models. IL-18 enhanced the engraftment of human CD8(+) effector T cells and promoted the development of xenogeneic graft versus host disease (GVHD). In marked contrast, IL-18 had reciprocal effects on the engraftment of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in the xenografted mice. Adoptive transfer experiments indicated that IL-18 prevented the suppressive effects of Tregs on the development of xenogeneic GVHD. The IL-18 results were robust as they were observed in two different mouse strains. In addition, the effects of IL-18 were systemic as IL-18 promoted engraftment and persistence of human effector T cells and decreased Tregs in peripheral blood, peritoneal cavity, spleen and liver. In vitro experiments indicated that the expression of the IL-18Ralpha was induced on both CD4 and CD8 effector T cells and Tregs, and that the duration of expression was less sustained on Tregs. These preclinical data suggest that human IL-18 may have use as an adjuvant for immune reconstitution after cytotoxic therapies, and to augment adoptive immunotherapy, donor leukocyte infusions, and vaccine strategies.
Animals, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Female, Gene Expression Regulation, Graft vs Host Disease/metabolism, Humans, Interleukin-18/metabolism, Male, Mice, Mice, Inbred NOD, Mice, SCID, Models, Biological, Neoplasm Transplantation, T-Lymphocytes, Regulatory/immunology, T-Lymphocytes, Regulatory/metabolism
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