Functional and molecular characterization of resident CD4+ T cells in lymphoid organs

• Applicant: Professor Dr. Oliver Pabst, since 8/2017
• Subject Area: Immunology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 298686481

Regulation of effector/memory T cell migration is essential for effective immune responses. However, due to highly dynamic nature of lymphocyte circulation, conventional methods can be insufficient to investigate certain aspects of T cell migration, especially egress of effector/memory T cell egress from lymphoid organs. To address these challenging aspects of lymphocyte circulation, we established novel in vivo cell tracking methods and successfully used these methods to unravel novel aspects of lymphocyte circulation. These techniques allowed us to identify a previously overlooked population of lymphoid-tissue resident effector/memory CD4+ T cells. These cells form 30-50% of all effector/memory CD4+ T cells in lymph nodes and Peyers patches and possess a distinct T cell receptor repertoire compared to other populations of effector/memory cells. Under homeostatic conditions, this population stays in lymphoid organs for at least four weeks and expresses low levels of S1pr1, the central receptor for lymphocyte egress. Despite these initial findings, many important and basic questions about this hitherto unappreciated immune cell population remain. In this project, we aim to further characterize resident CD4+ T cells in lymph nodes and Peyers patches. We hypothesize that, similarly to non-lymphoid tissue resident T cells; lymphoid tissue resident CD4+ T cells provide crucial protective functions during secondary immune responses due to their strategic positioning after primary immune responses. Firstly, we will try to describe cell types and molecular factors such as antigen and cytokines involved in the induction and maintenance of resident T cells in lymphoid organs. Secondly, developmental history of these cells will be analyzed as to where and when they are primed during immune responses. Thirdly, T cell-intrinsic molecular mechanisms contributing to the residency of resident CD4+ T cells will be investigated. Lastly, we will delineate functional contributions of this major but overlooked T cell population to immune responses. This project will not only provide valuable insights into generation and functions of resident CD4+ T cells in lymphoid organs but also open new avenues for T cell migration research.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Milas Ugur, until 7/2017