Hartmut Wekerle, Max Plank Institute of Neurobiology, Germany

Hartmut Wekerle

Hartmut Wekerle was director and member of the Max Planck Institute of Neurobiology in Martinsried, Germany (1988 - 2012). In 2012 Wekerle was awarded a Hertie Senior Professorship, and he now leads an Extended Emeritus Group. Hartmut Wekerle's scientific research focuses on the mechanisms initiating and driving multiple sclerosis and its experimental models, which imply autoimmune attack against the nervous system. Wekerle's work led to the identification of brain reactive autoimmune T lymphocytes in the immune system. Most recently, he identified the commensal bacterial gut flora as a factor triggering the pathogenic potential of immune cells. He develops and uses new imaging approaches to detail the mechanisms of autoimmune T cell migration into the brain. Wekerle has received numerous awards, including the Jung Prize, Zülch Prize, Koetser Prize, Charcot Award (Multiple Sclerosis International Federation), Grand Prix Louis D. (Institut de France), and a Koselleck Award (Deutsche Forschungsgemeinschaft). Wekerke holds an Honorary Professorship of the University of Munich and Honorary Doctorates of the Universities of Hamburg and Würzburg. Wekerke is a member of the German Academy of Science (Leopoldina), Honorary Member of the Société Française de Neurologie and Honorary Member of the Cuban Neuroscience Society.

Presentation abstract

CNS phagocytes presenting myelin autoantigen direct autoimmune T cells into the target tissue
Professor Hartmut Wekerle, MD1 and Naoto Kawakami, PhD2
Max-Planck Institute of Neurobiology1 and Munich University Biomedical Center2
82152 Martinsried, Germany
Email: hwekerle@neuro.mpg.de
Email addresses are provided for information in connection with the authors presentation only. Please do not mail credit card information under any circumstances.

A prevailing hypothesis considers multiple sclerosis as an autoimmune disease driven by self-reactive immune cells, which sit as dormant residents in the healthy immune repertoire, but unfold their auto-aggressive potential only upon pathogenic activation. Activated in the peripheral immune system, the effector cells take a complicated journey through the lymphatic system before they cross the blood-brain-barrier to infiltrate tissues of the CNS. The mechanistic details of this concept are based on observations in experimental animal models.

Studies of spontaneous experimental autoimmune encephalomyelitis models indicate that the autoimmune process is initiated in the gut-associated lymphatic tissue, where the immune system interacts with the commensal microbiota. Combining T cell mediated experimental autoimmune encephalomyelitis with two-photon microscopy, and genetic fluorochrome markers, we have followed activation events of pathogenic T cells from initial interactions in the gut through the lymphatic system to their infiltration into the CNS. We used the FRET-based calcium indicator Twitch to indicate early activation events of T cells interacting with stroma cells in successive tissue milieus.

We noted in myelin specific T cells migrating through the intestinal lamina propria strong calcium activity, which might represent presentation of microbial structures mimicking the target autoantigen MOG. In the spleen, the subsequent destination of, where the activated T cells undergo profound transcriptional reeducation required for passage through the brain-blood barrier, the T cells establish brief contacts with local stroma, resulting in sporadic short-lived calcium spikes. The licensed T cells pass through the brain-blood barrier into the leptomeningeal space, where they encounter local phagocytes, which present myelin antigens, re-activate the newly arrived T cells, and seem to guide them into the CNS parenchyma. Parenchymal phagocytes – microglia and infiltrating macrophages, further activate the T cells, and initiate an inflammatory cascade which ultimately leads to destruction of myelin and the cognate axonal processes.

Funding: Max-Planck-Society, the Hertie Foundation, Deutsche Forschungsgemeinschaft.

Conflicts of interest: None


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Supporting Publications
Organised by
  • Elsevier
  • TLP
  • TLN
  • Autoimmune Encephalitis (AE) Alliance
  • Encephalitis Society
  • Treating Autism