David Klatzmann jointly discovered the AIDS virus and pioneered research into regulatory T cells, a research topic for which he was awarded funding from the European Research Council (ERC Advanced Grant) in 2012.
Can you tell us about your path and your main discoveries during your career?
After studying medicine and science, my first research projects focused on suppressor T lymphocytes, an extremely popular subject at the time. During this period, I had the opportunity to work on the case of the first AIDS patient in France, in 1981. I then redirected my research to focus on this area. My first major discovery involved evidencing the tropism and cytopathic effect of HIV, in 1983, thus demonstrating that it was the cause and not the consequence of immunodeficiency in patients. In 1984, I then demonstrated that the CD4 molecule was the HIV receptor.
I went on to join Richard Axel, in the United States, who was my scientific mentor, to work on identifying potential HIV coreceptors. I spent two extraordinary years over there, and met some outstanding researchers.
Back in Paris, in 1989, I focused on the use of retroviruses as therapeutic instruments, first in gene therapy, and then in vaccination. My second major contribution involved the development of a cytomegalovirus vaccine. It is now in clinical development and could be the first effective preventive vaccine.
After working on the elusive "suppressor T cells", I was naturally drawn to their rebirth as "regulatory T cells" (Treg) which modulate the immune response. My third major discovery involved demonstrating that low-dose interleukin-2 stimulates Tregs in humans, paving the way for a very promising therapeutic approach.
Which project did you receive an ERC grant for?
I was awarded this grant to work on what I believed to be the key question surrounding Tregs: their antigenic specificity. In other words, the aim was to identify the targets recognized by these cells. Finding the answer to this fundamental question would make it possible to identify antigen receptors of diagnostic interest (biomarkers for disease progression) or therapeutic interest (to generate genetically modified Tregs). This project is based on the recent developments in massive sequencing techniques.
Since the start of the project, we have faced a number of difficulties regarding these techniques. This led us to create a network of international experts to compare and identify the most suitable different technologies. We have now found the answers to these questions, and have begun the massive sequencing campaign which will generate the data to be analyzed. These data will yield the first major results for this project.
How has the ERC helped you move forward in your research?
The ERC forces researchers to think of breakthrough projects, involving major risk-taking, and offers them the resources necessary for projects, the costs of which are incompatible with the majority of calls for tenders. I would not have been able to work on this project without the ERC.
You work on extremely diverse subjects in your research; is this something you set out to do?
Yes, I have always thought of myself as a translational immunologist. I am interested in analyzing situations involving the immune system, understanding the mechanisms at work, and devising medical applications for these mechanisms. My dual medical and scientific culture allows me to approach a very wide range of research topics, with the necessary hindsight and perspective to be both innovative and productive. This also demands a great deal of personal investment, but I am lucky in that I am passionate about my work!
Find out more about David Klatzmann and his research work
David Klatzmann manages the Immunology - Immunopathology – Immunotherapy (I3) unit at Hôpital de la Pitié Salpêtrière (Paris). He is also in charge of the Immunopathophysiology team and the Biological Therapy and Immunology Clinical Investigation Center (CIC-BTi).