IL-15 but not IL-2 rapidly induces lethal xenogeneic graft-versus-host disease.
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.
Department 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.
Sameek
S
Roychowdhury
Bradley W
BW
Blaser
Aharon G
AG
Freud
Kerry
K
Katz
Darshna
D
Bhatt
Amy K
AK
Ferketich
Valerie
V
Bergdall
Donna
D
Kusewitt
Robert A
RA
Baiocchi
Michael A
MA
Caligiuri
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D017690:Cell Transplantation; D016207:Cytokines / Q000378:metabolism; D006086:Graft vs Host Disease / Q000209:etiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D014183:Transplantation, Heterologous
D000276:Adjuvants, Immunologic; D016207:Cytokines; D019409:Interleukin-15; D007376:Interleukin-2; D007371:Interferon-gamma