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Malignant catarrhal fever (MCF) is a lethal lymphoproliferative disorder of cattle and deer caused by infection with either Alcelaphine Herpesvirus-1 (AHV-1) or Ovine Herpesvirus - 2 (OHV-2). It was proposed that the viruses induce an interleukin-2 (IL-2) hyperproduction which is responsible for the lymphoid cell hyperplasia observed. The hyperplasia of lymph node cells was investigated by examining the growth characteristics of freshly explanted lymph node cells from AHV-1 infected rabbits. The lymph node cells had a higher thymidine uptake respective to control cultures in the first 24 hours. IL-2 increased viability and thymidine uptake and Con A did not stimulate these cells as expected. Very little IL-2 activity could be detected in supernatants from short term cultures using the CTLL-based bioassay. To establish a TR-PCR/immunoblot for the detection of rabbit IL-2 mRNA, IL-2 cDNA from Con A stimulated rabbit lymphocytes was cloned and partially sequenced. IL-2 transcripts could be detected in lymphoid cells from pyrexic rabbits with AHV-1 and in cells from control rabbits. Furthermore, it was shown that lymphoblastoid cell lines (LCL) derived from MCF-affected cattle did not transcribe IL-2. These data lead to the conclusion that IL-2 is involved in the acute state of MCF, but does not have a central role in the pathogenesis. Further characterisation of IL-2 dependent LCL showed that they responded weakly to Con A, were inhibited by Cyclosporin A and transcribed constitutively IL-4, IL-10, INFγ and TNFα, whereas no IL-1β mRNA could be detected. These data together with the results derived from the short term cultures of lymph node cells from AHV-1 infected rabbits clearly show that MCF inducing viruses alter the behaviour of lymphoid cells. The possible interference of OHV-2 and AHV-1 with transductional pathways, the expression of IL-2R and the activation of self-reacting lymphocytes are discussed. |
