Exhausted T cells have long been considered a hallmark of chronic infections and cancer, arising from persistent antigen exposure and inflammatory cues. Surprisingly, we have recently uncovered that exhaustion-like T-cell states can also be induced during acute infection. We will outline the cellular and molecular mechanisms that drive this differentiation, including the balance of antigen strength, cytokine milieu, and inhibitory receptor signaling, and discuss the functional consequences for pathogen control and memory formation. In the second part, we will explore the biology of tissue-resident T cells, focusing on their fate decisions, long-term maintenance, and spatial dynamics during secondary influenza infection. Notably, our data indicate that a substantial fraction of resident T cells is generated largely de novo upon re-infection, reshaping local immunity.
About the speaker
Dietmar Zehn is full professor and head of chair of Physiology and Immunology at the Technical University of Munich and the Executive Director of the new TUM Center for Infection Prevention. He obtained an MD/PhD degree from the Charité – Medical School of the Humboldt University in Berlin, completed a postdoctoral fellowship with M.J. Bevan at the University of Washington, and held an assistant professorship at the University of Lausanne. His research focuses on the molecular and cellular mechanisms guiding T cell differentiation in acute and chronic infections and tumors. Specifically, he aims to uncover the processes that lead to the development and maintenance of exhausted T cells and to understand their biological function. He has been awarded two grants from the European Research Council (ERC) and received the ACTERIA/EFIS Early Career Research Prize. Recently, he successfully secured competitive, national funding for a new research building, the TUM Center for Infection Prevention.
