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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.


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IMMUNOBIOLOGY
Brief report

IL-15 but not IL-2 rapidly induces lethal xenogeneic graft-versus-host disease

Sameek Roychowdhury, Bradley W. Blaser, Aharon G. Freud, Kerry Katz, Darshna Bhatt, Amy K. Ferketich, Valerie Bergdall, Donna Kusewitt, Robert A. Baiocchi, and Michael A. Caligiuri

From 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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