During the course of my career, I have worked in many different laboratories, in several different countries and have been interested in various scientific topics all of which somehow have to do with immunology.
My scientific career began with my medical doctoral thesis, supervised by Prof. Dr. med. Gerhard Kolde in the Department of Dermatology, Charité, Humboldt University of Berlin. Because of a bet between my supervisor and a professor at a different German University, I ended up studying neutrophilic granulocytes, a type of white blood cell that is important during acute immune responses. He favored the idea that these cells die by programmed cell death (apoptosis) rather than “random” cell death (necrosis) during the resolution of cutaneous immune complex vasulitis, which is a self-limiting inflammation of the small blood vessels of the skin that manifests as a rash on the lower parts of the legs. I found that these cells die by a non-classical form of programmed cell death.
The work in the laboratory and the constant thrill of thinking about possible answers to questions that nobody knows the answers to made me continue with science in Prof. Karin Moelling’s laboratory at the University of Zurich. Dr. Jochen Heinrich taught me molecular cloning and we developed a DNA plasmid-based therapy that inhibited blood vessel growth. The idea was to starve tumors by reducing their blood supply. Because inhibiting blood vessel growth alone only inhibited tumor growth for a short period of time, we added DNA plasmids encoding proinflammatory cytokines to the treatment and this proved to have a much more potent effect on tumor growth.
Then, I became interested in the pathogenesis of Epstein-Barr virus (EBV) infection. EBV causes the so-called “kissing disease” that is usually seen in adolescents and plays a role in certain types of tumors. Prof. David Nadal at the University Children’s Hospital of Zurich, co-workers and I found that the higher immune activation in immunologically mature peripheral blood mononuclear cells, as compared to “immature” cord blood mononuclear cells, suppressed lytic EBV infection (more precisely, BZLF1 expression), but supported latent EBV infection. We concluded that immune activation may favor the transformation/immortalization of EBV infected cells and thereby may increase the risk of EBV-associated tumor development.
I then moved to San Francisco to work with Prof. (Mike) McCune at UCSF. I became interested in immunological memory, more specifically, T cell memory. It is not known whether long-term immunological T cell memory is maintained by constant low-level proliferation of certain T cell subsets or by long-lived memory T cells that are able to remain in a quiescent state over a very long period of time. Using in vivo stable isotope labeling in humans, we found that two different memory-phenotype CD8+ T cells have a long lifespan and that one of these phenotypes, which expresses CD57, accumulates in the face of HIV disease progression, whereas the other appears to have a shorter half-life and reduced abundance, particularly in HIV infected individuals with high viral loads. The loss of the latter cells may be responsible in part for the progressive loss of T cell memory function during progressive HIV infection.
We also studied antigen-specific naïve and memory CD4+ T cell turnover in vivo using stable isotope labeling in a TCR transgenic mouse model during continuous peptide administration of up to 1.5 months. This project has been dormant for a while, but will be completed soon.
Both of these studies were and are only possible because of the long-standing collaboration between Mike McCune’s laboratory at UCSF and Marc Hellerstein’s laboratory at the University of California Berkeley.