Production and utilization of interleukin-15 in malignant catarrhal fever.
Malignant catarrhal fever (MCF) is an often fatal lymphoproliferative disease of ungulates caused by either alcelaphine herpesvirus-1 (AlHV-1) or ovine herpesvirus-2 (OvHV-2). The pathogenesis of MCF is poorly understood, but appears to involve an auto-destructive pathology whereby cytotoxic lymphocytes destroy areas of a variety of tissues. The cytokine interleukin-15 (IL-15) is involved in the development and maintenance of cytotoxic lymphocytes and may therefore have a role in the pathogenesis of MCF. Virus-infected large granular lymphocytes (LGLs) were obtained from the tissues of rabbits infected with AlHV-1 or OvHV-2. These cells exhibited a similar proliferative response to IL-15 and to IL-2 in culture, but their content of the activated cytotoxic enzyme (BLT-esterase) was maintained at higher levels in the presence of IL-15 compared with IL-2. The LGLs did not express IL-15 mRNA or produce IL-15 protein. By contrast, there was abundant expression of IL-15 mRNA and protein in affected tissues. IL-15 production was associated with necrotic lesions of the mesenteric lymph node and appendix of OvHV-2-infected rabbits, but was not found in the same tissues of rabbits infected with AlHV-1 in which there were no necrotic lesions. The cellular source of the IL-15 was predominantly lymphoid cells that did not express B cell or monocyte-macrophage markers. Only a few IL-15+ cells (<10%) co-localized with pan-T cells or CD8+ T cells. The abundance of IL-15 in tissue with lesions of MCF suggests that this cytokine may have a role in the pathogenesis of MCF.
Anderson
I E
IE
Moredun Research Institute, Edinburgh, Scotland, UK.
Deane
D
D
Swa
S
S
Thomson
J
J
Campbell
I
I
Buxton
D
D
Wei
X-Q
XQ
Stewart
J
J
Russell
G
G
Haig
D M
DM
D000818:Animals; D001065:Appendix / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004950:Esterases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D008304:Malignant Catarrh / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D018144:Rhadinovirus / Q000502:physiology*; D012697:Serine Endopeptidases / Q000378:metabolism
D015415:Biomarkers; D019409:Interleukin-15; D007376:Interleukin-2; D012333:RNA, Messenger; D004950:Esterases; C022635:serine esterase; D012697:Serine Endopeptidases