IL-15 but not IL-2 rapidly induces lethal xenogeneic graft-versus-host disease
Sameek Roychowdhury1, Bradley W Blaser, Aharon G Freud
1Department of Molecular Virology, Immunology, and Medical Genetics, the Medical Scientist Program, the Integrated Biomedical Science Graduate Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Abstract:
Interleukin-2 (IL-2) and IL-15 are structurally related cytokines that share receptor components but display markedly different effects in multiple in vivo model systems. Here we demonstrate that IL-15 but not IL-2 exacerbates xenogeneic graft-versus-host disease (X-GVHD) in severe combined immunodeficient murine recipients of human peripheral-blood lymphocytes (hu-PBL-SCID). Treatment of hu-PBL-SCID mice with IL-15 resulted in rapid fatality, lymphocytic infiltrations in the liver, lung, and spleen consistent with X-GVHD, and a marked expansion of human CD4+ and CD8+ T cells compared with controls. Depletion of human T cells in vivo abrogated the lethality of IL-15 treatment. To our knowledge, these data are the first to demonstrate in vivo activation and expansion of human T lymphocytes in response to IL-15 with concomitant exacerbation of human T-cell-mediated X-GVHD.
