Session II: Networking: a question of balance

Thursday March 30, after lunch

13.45                   Michelle Linterman, Cambridge, United Kingdom mlinterman.png
"Follicular regulatory T Cells and the germinal centre response"

Ine Vanderleyden1, Wim Pierson1, Meryem Aloulou2, Nicolas Fazilleau2, Michelle A. Linterman1
1Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
2Centre de Physiopathologie de Toulouse Purpan (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM), U1043, Toulouse, F-31300, France; Centre National de la Recherche Scientifique (CNRS), U5282, Toulouse, F-31300, France; Université de Toulouse, Université Paul Sabatier, Toulouse, F-31300, France.

T follicular regulatory (Tfr) cells form in response to vaccination when Foxp3+ precursors co-opt the Tfh cell differentiation pathway to acquire a Tfh-like profile, and migrate into the B cell follicle where they act as suppressor cells within the Germinal Centre (GC).  Investigation into Tfr has only begun in earnest in the past few years; consequently, there are a number of fundamental questions about their biology that need to be answered. We know Tfr cells control the size of the GC response in vivo, but we do not know their antigen specificity, whether they control self or non-self responses, if they are required for the quality of the GC response or which cells they exert their suppressive effects on. We have used a number of approaches to address these important gaps in our knowledge of Tfr cell biology. We show that Tfr cells can be specific for the immunising antigen, irrespective of whether it is a self or non-self antigen. Moreover, we found that Tfr cells can differentiate from induced regulatory T cells if immunisation is performed with an adjuvant that supports T cell plasticity, suggesting that Tfr cell formation is more malleable than originally appreciated.

Funding provided by the European Research Council (637801 TWILIGHT)

14.30                   Bart Jacobs, Rotterdam, The Netherlands
"Post-infectious nerve inflammation: consequences of disrupted networks"bjacobs.jpg

Bart C. Jacobs
Departments of Immunology and Neurology, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands, e-mail:

Post-infectious disorders are the consequence of a disrupted balance in the normal immunity to infections. The nervous system, a network itself which is highly dependent on nerve cell membrane integrity for normal function, is especially vulnerable for such excessive immune responses. Various post-infectious disorders of the central and peripheral nervous system have been identified. The Guillain-Barré syndrome (GBS) is one of the most severe forms since previously healthy person may develop a full paralyses of the limbs and respiratory failure within 1 day, that may be fatal if left medically unattended. Patients are treated with intravenous immunoglobulin or plasma exchange, alongside supportive care. GBS is an acute peripheral neuropathy that yearly affectis 100,000 persons worldwide. GBS in all cases is preceded by an infection (or vaccination), that induces an aberrant immune response targeting peripheral nerves and spinal nerve roots. Campylobacter jejuni is the predominant trigger of GBS, in addition to Epstein-Barr virus, cytomegalovirus and Mycoplasma pneumoniae, and more recently to emerging pathogens as hepatitis E virus and Zika virus. In case of C. jejuni it is evident that GBS is caused by carbohydrate  mimicry between microbial and nerve glycolipids that triggers in susceptible persons a cross-reactive and neurotoxic antibody response. Sialic acids in the lipo-oligosaccharides of C. jejuni enhance the human dendritic cell response and this TLR-4 mediated response is intrinsically increased in patients with GBS. This host factor in part explains why these infection trigger the onset of GBS only a very small proportion of persons. At present it is unknown if similar mechanisms play a role in GBS after other types of infection. The variety of preceding infections and clinical variant forms of GBS may explain why the response to treatment is highly variable. Clinical outcome of GBS is still poor since 25% progresses after treatment, 20% is unable to walk after six month, and the majority suffers from residual deficits or complaints. In the ongoing International GBS Outcome Study (IGOS) a consortium from >150 hospitals and universities from 19 countries has raised an extensive data/biobank  that is available to identify the factors that determine the disease onset and course. The final goal is to understand the pathogenesis in each patient with GBS and provide a more rational and personalized treatment.

15.15                  Tea break

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