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closeMissing references and comment
Posted by davemckh on 02 Sep 2009 at 14:33 GMT
In this report by Meier-Trummer etal, two important findings of the microarray analysis of OvHV-2 malignant catarrhal fever (MCF)-affected cattle lymphoid tissue were (1) low abundance of the IL-2 transcript and (2) high abundance of the transcript for the T cell-associated kinase Lck. We were therefore surprised that two key references addressing both these phenomena in MCF were not cited. The first of these by Alex Schock, Collins, B and Reid, H (Vet Immunol Immunopathol 1998 66:67-81) described a lack of IL-2 mRNA in OvHV-2-infected large granular lymphocyte T cells (LGL) obtained from MCF affected rabbits. This was against a background of mRNA expression for a range of other cytokines expressed by the LGLs. The LGLs represent virus-infected cells from MCF-affected animals and are important cells for the study of MCF. The authors speculated on the possible consequences of a lack of IL-2 in MCF pathogenesis. The second omitted reference is by Sandi Swa , Wright, H, Thomson J, Reid H and Haig D (Immunology 2001, 102:44-52). In this study, the authors reported that OvHV-2 or AlHV-1-infected LGL constitutively produced a high level of the lck transcript, which is normally tightly regulated in ‘normal uninfected’ T cells shortly after activation. The consequence of this for the pathogenesis of MCF was discussed. The missing references coupled with the microarray study allow us to speculate that viral mechanisms within infected cells are responsible for both phenomena (low Il-2, high lck) and that virus infected cells have an important role in the pathogenesis of MCF, rather than a few virus infected cells having an indirect effect on pathogenesis by way of activating uninfected cells in the various MCF-affected tissues. Importantly, the low abundance of IL-2 and high level expression of lck in MCF has been known for some time.
Prof. David Haig, SVMS, University of Nottingham.
RE: Missing references and comment
Mathias_Ackermann replied to davemckh on 08 Sep 2009 at 09:00 GMT
The authors of the present article thank Prof. Haig for his comments on our publication. Indeed, he makes a very good point and we are glad to have published in a type of Journal that makes such after-publication discussions possible at all.
Both of the two publications mentioned in Prof. Haig’s comment are based on the use of large granular lymphocyte T cells (LGL) obtained from MCF affected animals. It is understood that OvHV-2-infected LGLs were not primary but had been cultivated over weeks at high density and supported by feeder cells as well as exogenous IL-2 (REF 44 in our article). Only later on, LGLs may become independent of IL-2. Similarly, the AlHV-1-LGLs were stabilized after approximately 8 weeks of culturing. It is quite possible that specialized cells may shape their phenotype during the time of culturing, especially since they are kept out of their complex in-vivo-environment. Moreover, the viral gene expression pattern in cultured LGLs (REF 29 in our article) differs from the viral gene expression pattern as determined in our study, where uncultivated cells were analyzed, directly obtained from the lymph nodes of cattle with MCF. Specifically, we determined in our context a predominantly latent viral gene expression pattern, whereas the cultured LGLs displayed mRNAs indicative for a mixture of latenly- and productively-infected cells (REF 29 in our article).
On this background, it is truly amazing to see that, despite of all those caveats, the former ex vivo studies were able to describe a cellular phenotype that shares obviously many similarities with the in vivo situation described in our present article.
In addition to the genes addressed in Prof. Haig’s comment, we have listed a total of 6.300 probe sets that were significantly affected in the context of MCF, most of which were not discussed extensively in our paper. Thus, we may look forward to receiving more comments on our work.