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

Dietmar Zehn

Das "HZI-Kolloquium" ist eine wissenschaftliche Vorlesungsreihe zu dem international anerkannte Experten aus dem Bereich Infektionsforschung ans Helmholtz-Zentrum für Infektionsforschung, Braunschweig, eingeladen werden. In Vorträgen geben die Gastsprecher Einblicke in ihre aktuellen Arbeiten. Im Anschluss besteht die Möglichkeit zu einer offenen Diskussion. Wir laden alle interessierten Wissenschaftler zur Teilnahme an diesem Kolloquium herzlich ein.

  • Überblick

    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. 


    Datum: 11.02.2015, 18:00

    Veranstaltungsort

    HZI

    Gebäude und Raum

    Forum X0.13

    Referent

    Dietmar Zehn - Swiss Vaccine Research Institute

    Gastgeber

    Dirk Heinz