T-cell development and activation in humanized mice lacking mouse major histocompatibility complexes
Year: 2024
Type: preprint
Abstract: Humanized mice transplanted with CD34 + hematopoietic progenitor cells (HPCs) are used to study human immune responses in vivo . However, the mismatch between the mouse major histocompatibility complexes (MHCs) and the human leukocyte antigens (HLAs) is not optimal for T-cell development and can trigger xenograft reactivity. We evaluated human T-cell development in NOD.Scid.Gamma mice lacking expression of MHC class I and II (NSG-DKO). Human leukocyte engraftment was detectable at 8 weeks post-transplantation. Human CD4 + and CD8 + T-cells were detectable in blood, thymus, bone marrow and spleen of humanized NSG-DKO mice for up to 20 weeks post-transplantation. Further, we evaluated the effects of lentiviral vector (LV) systemic delivery of HLA-A*02:01, HLA-DRB1*04:01, human GM-CSF/IFN-α and the human cytomegalovirus gB antigen. LV delivery promoted development and activation of human central memory, αβ and γδ T-cells with amplifications of the T-cell repertoire. LV administration unleashed multiple reactome pathways such as type-I interferon responses, cell cycle and metabolic processes. In summary, development of human T-cells in humanized mice does not rely on mouse MHCs and can be boosted systemically via LV administration.
Authors: Milita Darguzyte, Philipp Antczak, Daniel Bachurski, Patrick Hoelker, Nima Abedpour, Rahil Gholamipoorfard, Hans A. Schlößer, Kerstin Wennhold, Martin Thelen, Maria Garcia-Marquez, Johannes König, Andreas Schneider, Tobias Braun, Frank Klawonn, Michael Damrat, Masudur Rahman, Jan-Malte Kleid, Sebastian J. Theobald, Eugen Bauer, Constantin von Kaisenberg, Steven Talbot, Leonard Shultz, Brian Soper, Renata Stripecke
Institutions: University of Cologne, University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Medizinische Hochschule Hannover, Ostfalia University of Applied Sciences, Helmholtz Centre for Infection Research, German Center for Infection Research, Jackson Laboratory
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4393548712