Dietmar Zehn - "T-cell differentiation in chronic infection – functional adaptation or exhaustion?"

Dietmar Zehn

The "HZI Colloquium" is a scientific lecture series at the Helmholtz Centre for Infection Research in Braunschweig, organized to host internationally renowned experts from the field of infection research. Invited guest speakers present their current research activities to a scientific audience. The presentation is followed by an open discussion. We cordially invite interested scientists to take part in this colloquium.

  • Overview

    Concerning your latest results, what happens to specific T cells after an infection or during a persisting infection?
    It is widely accepted that actively persisting chronic infections coincide with the
    appearance of dysfunctional or “exhausted” T cells. Contrasting this concept in
    its simplest form, we recently made several observations indicating that T cells
    undergo differentiation and possibly a form of functional specialization in chronic infections rather than becoming non-functional. We demonstrated for instance that T cells with an exhausted phenotype do not inevitably inherit a survival or expansion deficit and we uncovered that even functional memory T cells are formed in chronic infections which transmit an exhausted phenotype.

    What are the T cell characteristics you are looking for?
    We are interested in understanding what determines if T cells acquire a normal or an exhausted phenotype and how differences in antigen exposure impact this decision. To do so, we generated recombinant strains of chronic LCMV clone-13 which express altered peptide ligands for P14 TCR transgenic T cells. With the help of these strains, we can illustrate that the frequency of TCR engagement and less significantly the strength of TCR stimulation impacts the formation of the chronic infection phenotype.

    How could a better knowledge of T cell differentiation help in understanding infectious diseases?
    We proposed that chronic infections generate T cells with reduced effector function and which cause less immunopathology than T cells formed in acute infections. Presently, we are using new experimental strategies and complementary bio-informatic approaches to extrapolate molecules involved in generating “exhausted” or normal T cells. We believe this knowledge could be used to selectively enforce or attenuate T cell responses in acute or chronic infections. 


    Date: 11.02.2015, 18:00

    Location

    HZI

    Building and room

    Forum X0.13

    Speaker

    Dietmar Zehn - Swiss Vaccine Research Institute

    Host

    Dirk Heinz