Poster Presentation CD1-MR1 2024

Novel NK-like T cells Reinvigorating Dysfunctional CD8 T-cells in Chronic Viral Infection and Cancer (#210)

Anna F. Lindemann 1 , Konstantinos Symeonidis 1 , Chintan Chhatbar 2 , Paula Poier 1 , Carl Philipp Hackstein 1 3 , Olaf Utermöhlen 4 , Percy A. Knolle 3 , Marco Prinz 2 , Zeinab Abdullah 1
  1. Institute of Molecular Medicine & Experimental Immunology, University Hospital Bonn, Bonn, Germany
  2. Institute of Neuropathology, University of Freiburg, Freiburg, Germany
  3. Institute of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany
  4. Institute for Medical Microbiology, Immunology and Hygiene, University Hospital Cologne, Cologne, Germany

Besides the NKT and MAIT cells, NK-like T cell family encompasses a heterogeneous population of cells most of which remain largely unknown. By combining scRNA-seq, fate mapping and transgenic mouse models, we defined a novel population of NK-like T helper cells (referred to as NLCs) that are nonrestricted to CD1d, MR1 and microbiome-derived antigens, lack γδTCR expression, and reside predominantly within the vasculature in the liver. Although, NLCs are not restricted to the known classical and non-classical MHC molecules, they require the thymus for their development. Compared to other T cells in the liver, NLCs depict a unique transcriptional signature, moderate cytotoxic capacity and express molecules that are so far have been described only in NK cells. Upon viral infection or TCR stimulation, NLCs release IL-2, IFNg, CCL3, CCL5 and XCL1 indicating T helper like and innate lymphocytes functions. Importantly, intra-tumoral injection or systemic transfer of NLCs from healthy mice reinvigorated dysfunctional antigen-specific CD8 T cells and promoted cancer immune control and viral clearance in chronic LCMV infection respectively. Collectively, our study identifies a previously unknown T helper cell subset that may be exploited to develop novel immune therapies.