Selected articles June 2014:
Expression of costimulatory factors on dendritic cells to be used in anti-tumour vaccine
High functional CD70 expression on alpha-type-1-polarized Dendritic cells from patients with chronic lymphocytic leukaemia
K. Junevik, O. Werlenius, L. Fogelstrand, A. Karlsson-Parra, P.-O. Andersson
In a study performed in the PO Andersson lab at Sahlgrenska University Hospital in Gothenburg, means to optimize the method of using antigen-loaded dendritic cells (DCs) as anticancer vaccine, was investigated. A DC vaccine should elicit an effective T cell anti-tumour response. To do this, a DC needs to provide an array of functions, such as antigen-presentation, costimulation, induction of effector functions and expression of receptor with tumour-specific homing properties.
The most frequently described DC vaccine today is being matured with a cocktail containing prostaglandin E2, and they are called PGE2DCs. However, these cells tend to give an insufficient Th1 response. Instead, it has been suggested that alpha-type-1 polarized DCs (called aDC1) give a more appropriate activation of effector cells. It has also been shown that the costimulatory factor CD70 appears to be essential for optimal DC function. So far PGE2 is suggested as one of the most important factors for the induction of CD70 on DCs. The present investigation shows that aDC1s express CD70 equally good as PGE2DCs.
Katarina Junevik was a PhD student in the group when the study was conducted. She defended her thesis in September 2013, and she did almost all the laboratory work. The study design and writing of the paper was done together with her supervisor PO Andersson
– The most fun part was to create a method and make it work, like we did. To be able to with so few cells still create a milieu where we could analyse the production of cytokines was fascinating, she says.
Expression of costimulatory surface receptors after dendritic cell maturation appears to be a dynamic process. To establish an optimal anti-tumour DC vaccine protocol, proper timing for the determination of such receptors are crucial.
Removal of IFNg and perforin tips the balancing race between virus and host in favour of the virus
IFNγ and perforin cooperate to control infection and prevent fatal pathology during persistent gammaherpesvirus infection in mice
C. Bartholdy, M. Høgh-Petersen, P. Storm, P. J. Holst, C. Ørskov, J. P. Christensen and A. R. Thomsen
The cooperation of IFN-gamma and perforin to control an viral infection and prevent immune-mediated as well as virus-mediated pathology is shown in this study by Christina Bartholdy and co-workers.
Christina Bartholdy was a PostDoc in the group at the time of the study, and now works as a senior scientist at Novo Nordisk A/S. I ask her about her role in the study.
– I was the main driver of the research process including planning and conducting the majority of the experiments, interpreting the results, designing follow up experiments and writing the paper. However, the whole process that led to this publication has been a close and fruitful collaboration with especially professor Allan Randrup Thomsen, but also with significant scientific contributions from the other authors.
Inspired by a paper by Dutia et al. showing that MHV68 infection of IFNgR-/- mice lead to splenic atrophy and fibrosis, and that this pathology could be reversed by depletion of CD8 T cells, the initial research question was to analyse whether this seemingly pathological role of CD8 T cells was mediated by perforin-mediated killing of virus infected cells. Much to the researchers´ surprise, they observed that although absence of perforin effectively prevents splenic atrophy, it likewise results in an inability to control the virus infection, which leads to chronic immune activation, significant immunopathology and finally complete destruction of the normal architecture of the spleen. In other words, removal of both IFNγ and perforin seems to tip the balancing race between the virus and the host in favour of the virus, which subsequently results in fatal pathology most likely due to chronic immune activation.
What was most fun during the work that led to this paper?
– One exciting and challenging thing about biological research is that the pathway from scientific hypothesis to conclusion is rarely as straight forward as you initially think. This has indeed also been true for this project. Interpreting our surprising findings and designing new experiments to further address the biology behind has been really fun and exciting, Christina Bartholdy concludes.