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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2433-2435. Prepublished online as a Blood First Edition Paper on June 23, 2005; DOI 10.1182/blood-2005-04-1597.
IMMUNOBIOLOGY IL-15 but not IL-2 rapidly induces lethal xenogeneic graft-versus-host diseaseFrom the Department of Molecular Virology, Immunology, and Medical Genetics, the Medical Scientist Program, the Integrated Biomedical Science Graduate Program, the Department of Internal Medicine, the Division of Hematology/Oncology, the Division of Epidemiology and Biostatistics, the Department of Veterinary Preventive Medicine, and the Department of Veterinary Biosciences, the Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
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. (Blood. 2005;106:2433-2435)
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