Leukocyte Dynamics (Kastenmüller Lab)

Our laboratory investigates the spatiotemporal organization of the immune system. We seek to understand how immune information is transmitted, integrated, and regulated through dynamic cellular circuits to generate protective immunity while maintaining peripheral tolerance.

Rather than studying immune cells in isolation, we aim to uncover the principles by which immune cells cooperate across space and time to coordinate adaptive immune responses.

Lymphocyte cooperation

Effective immunity depends on continuous communication between lymphocytes and antigen-presenting cells. Our work has shown that CD4⁺ T cell help is delivered through a multistep priming process that actively instructs CD8⁺ T cell differentiation. We are currently investigating how these cellular communication networks regulate T cell fate during chronic infection and cancer, with a particular focus on the mechanisms that instruct T cell exhaustion.

Dendritic cell development and function

Dendritic cells continuously adapt to their tissue environment and acquire specialized functional states that are only partially reflected by their transcriptional profiles. We investigate how dendritic cell differentiation and activation are regulated, how tissue-specific microenvironments shape their function, and how distinct dendritic cell states instruct immunity, tolerance, and T cell differentiation.

Tissue-adapted lymphocytes

Many lymphocyte populations traditionally considered tissue-resident – including unconventional T cells and tissue-adapted regulatory T cells – appear to continuously migrate between tissues and lymphoid organs. We investigate how these cells differentiate, why they recirculate, and how their dynamic behavior contributes to tissue homeostasis, repair, and immune regulation.

Kastenmueller link pubmed: https://pubmed.ncbi.nlm.nih.gov

Selected Articles

1. A distinct priming phase regulates CD8 T cell immunity by orchestrating paracrine IL-2 signals. Katarzyna Jobin, Deeksha Seetharama, Lennart Rüttger, Cloe Fenton, Ekaterina Kharybina, Annerose Wirsching, Anfei Huang, Konrad Knöpper, Tsuneyasu Kaisho, Dirk H. Busch, Martin Vaeth, Antoine Emmanuel Saliba, Frederik Graw, Alain Pulfer, Santiago F. Gonzalez, Dietmar Zehn, Yinming Liang, Milas Ugur, Georg Gasteiger and Wolfgang Kastenmüller.  Science 388,eadq1405(2025).DOI:10.1126/science.adq1405
2. Resident regulatory T cells reflect the immune history of individual lymph nodes. Kaminski A, Hager FT, Kopplin L, Ticconi F, Leufgen A, Vendelova E, Rüttger L, Gasteiger G, Cerovic V, Kastenmüller W, Pabst O, Ugur M. Published in Science Immunology 2023. DOI: 10.1126/sciimmunol.adj5789
3. Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks. Ugur M, Labios RJ, Fenton C, Knöpper K, Jobin K, Imdahl F, Golda G, Hoh K, Grafen A, Kaisho T, Saliba AE, Grün D, Gasteiger G, Bajénoff M, Kastenmüller W., Immunity. 2023 Aug 8;56(8):1778-1793.e10. doi: 10.1016/j.immuni.2023.06.020. Epub 2023 Jul 17.
4. CD4⁺ T cell-induced inflammatory cell death controls immune-evasive tumours, Bastian Kruse,  Anthony C. Buzzai, Naveen Shridhar, Andreas D. Braun, Susan Gellert, Kristin Knauth, Joanna Pozniak, Johannes Peters, Paulina Dittmann, Miriam Mengoni, Tetje Cornelia van der Sluis, Simon Höhn, Asier Antoranz, Anna Krone, Yan Fu, Di Yu, Magnus Essand, Robert Geffers, Dimitrios Mougiakakos, Sascha Kahlfuß, Hamid Kashkar, Evelyn Gaffal, Francesca M. Bosisio, Oliver Bechter, Florian Rambow, Jean-Christophe Marine, Wolfgang Kastenmüller, Andreas J. Müller & Thomas Tüting, nature. 2023; June 14; doi: 10.1038/s41586-023-06199-x
5. Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes. Ataide MA, Knöpper K, Cruz de Casas P, Ugur M, Eickhoff S, Zou M, Shaikh H, Trivedi A, Grafen A, Yang T, Prinz I, Ohlsen K, Gomez de Agüero M, Beilhack A, Huehn J, Gaya M, Saliba AE, Gasteiger G, Kastenmüller W, Immunity. 2022 Aug 17:S1074-7613(22)00354-5. ; doi: 10.1016/j.immuni.2022.07.019
6. Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T cells in distinct cellular niches. Dähling S, Mansilla AM, Knöpper K, Grafen A, Utzschneider DT, Ugur M, Whitney PG, Bachem A, Arampatzi P, Imdahl F, Kaisho T,  Zehn D, Klauschen F, Garbi N, Kallies A,  Saliba AE, Gasteiger G, Bedoui S, Kastenmüller W. Immunity. 2022 Apr 12; 55(4):656-670.e8 ; doi: 10.1016/j.immuni.2022.03.006
7. BATF3 programs CD8+ T cell memory. Ataide MA, Komander K, Knöpper K, Peters AE, Wu H, Eickhoff S, Gogishvili T, Weber J, Grafen A, Kallies A, Garbi N, Einsele H, Hudecek M, Gasteiger G, Hölzel M, Vaeth M, Kastenmüller W. Nat Immunol. 2020 Nov;21(11):1397-1407. doi: 10.1038/s41590-020-0786-2.Open Access
8. Lymphatic Endothelial Cells Are Essential Components of the Subcapsular Sinus Macrophage Niche. Mondor I, Baratin M, Lagueyrie M, Saro L, Henri S, Gentek R, Suerinck D, Kastenmuller W, Jiang JX, Bajénoff M. Immunity. 2019 Jun 18;50(6):1453-1466.e4. doi: 10.1016/j.immuni.2019.04.002
9. Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis. Welz M, Eickhoff S, Abdullah Z, Trebicka J, Gartlan KH, Spicer JA, Demetris AJ, H. Akhlaghi H, Anton M, Manske K, Zehn D, Nieswandt B, Kurts C, Trapani JA, Knolle P, Wohlleber D, Kastenmüller W. Nat Comm 2018 Nov 15;9(1):4805. doi: 10.1038/s41467-018-07213-x.
10. CD8+ T Cells Orchestrate pDC-XCR1+ Dendritic Cell Spatial and Functional Cooperativity to Optimize Priming. Brewitz A, Eickhoff S, Dähling S, Quast T, Bedoui S, Kroczek RA, Kurts C, Garbi N, Barchet W, Iannacone M, Klauschen F, Kolanus W, Kaisho T, Colonna M, Germain RN, Kastenmüller W. Immunity 2017 Feb 21;46(2):205-219. doi: 10.1016/j.immuni.2017.01.003.
11. Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions. Eickhoff S, Brewitz A, Gerner MY, Klauschen F, Komander K, Hemmi H, Garbi N, Kaisho T, Germain RN, Kastenmüller W. Cell 2015 Sep 10;162(6):1322-37. doi: 10.1016/j.cell.2015.08.004.

Selected Review Articles

1. Concepts of GPCR-controlled navigation in the immune system. Lämmermann T, Kastenmüller W. Immunol Rev. 2019 May;289(1):205-231. doi: 10.1111/imr.12752
2. CD4+ T cell help in cancer immunology and immunotherapy. Borst J, Ahrends T, Bąbała N, Melief CJM, Kastenmüller W. Nat Rev Immunol. 2018 Oct;18(10):635-647. doi: 10.1038/s41577-018-0044-0.
3. Lymph node - an organ for T-cell activation and pathogen defense. Gasteiger G, Ataide M, Kastenmüller W. Immunol Rev. 2016 May;271(1):200-20. doi: 10.1111/imr.12399.
4. Dendritic cell-targeted vaccines - hope or hype? Kastenmuller W, Kastenmuller K, Kurts C, Seder RA. 2014. Nat Rev Immunol 2014 Oct;14(10):705-11. doi: 10.1038/nri3727.
5. Spatiotemporal Basis of Innate and Adaptive Immunity in Secondary Lymphoid Tissue. Qi H, Kastenmuller W, Germain RN. 2014. Annu Rev Cell Dev Biol 2014;30:141-67. doi: 10.1146/annurev-cellbio-100913-013254.
6. Foxp3+ Regulatory T-cells and IL-2: The Moirai of T-cell Fates? Gasteiger G, Kastenmuller W.. Front Immunol 2012 3: 179. doi: 10.3389/fimmu.2012.00179.

ERC Consolidator Grant: Spatio-temporal regulation of T cell priming