Tailored T-Cell Diversity

T cell responses are enormously diverse. Even among T cells responding to the same antigen, T cells have a range of different specialized roles in the response. This relates to differences in e.g. their cytokine production, longevity, migratory behavior, and capacity to kill, proliferate and self-renew.

Understanding how and when T cells diversify to adopt these different roles paves the way for influencing T cell fates in the context of immunotherapy.

Our lab combines advanced flow cytometry, single-cell omics, functional assays, in vitro work, in vivo studies in mice and analyses on human samples to study the diversification of T cells. Our work at the LIT focuses on T cell immunotherapy of cancer and inflammatory diseases. We aim 1) to device simple and cost-effective strategies to obtain high-granular information on a T cell’s functional state to further develop human immunomonitoring and 2) to advance our understanding of T cell diversification and effector mechanisms to engineer T cells with optimal properties.

Different models of T cell diversification

A complete list of publications can be found on PubMed:

https://pubmed.ncbi.nlm.nih.gov/?term=carmen+gerlach&sort=date

Here is a selection of the most important publications from the last few years:

Pokharel J*, Shryki I*, Zwijnenburg AJ, Sandu I, Krumm L, Bekiari C, Avramov V, Heinbäck R, Lysell J, Eidsmo L, Harris H, Gerlach C. The cellular microenvironment regulates CX3CR1 expression on CD8⁺ T cells and the maintenance of CX3CR1⁺ CD8⁺ T cells. Eur J Immunol. 2024 Jan; 54(1):e2350658. Epub 2023 Oct 19. PMID: 37816219

Zwijnenburg AJ, Pokharel J, Varnaitė R, Zheng W, Hoffer E, Shryki I, Comet NR, Ehrström M, Gredmark-Russ S, Eidsmo L, Gerlach C. Graded expression of the chemokine receptor CX3CR1 marks differentiation states of human and murine T cells and enables cross-species interpretation. Immunity. 2023 Aug 8;56(8):1955-1974.e10. PMID: 37490909

Pokharel J, Gerlach C. Linking asymmetric cell division, CD8⁺ T cell fate, and signal strength. Cell Rep. 2023 May 12;42(5):112548. PMID: 37178121

Van Gisbergen KPJM, Gerlach C. No-shows in T cell responses are frequent for clones of low T cell receptor affinity. Eur J Immunol. 2023 Jan 21:e2250305. PMID: 36680414

Al-Khabouri S, Gerlach C. T cell fate-mapping and lineage-tracing technologies probing clonal aspects underlying the generation of CD8 T cell subsets. Scand J Immunol. 2020 Dec;92(6):e12983. PMID: 33037653

Zwijnenburg AJ, Gerlach C. Exploiting allelic variation in CD8+ T cells. Immunity. 2019 May 21;50(5):1119-1121. PMID: 31117005

Eidsmo L, Gerlach C. Heavy water shedding light on antigen-specific T cell responses. Trends Immunol. 2018 Mar;39(3):170-172. PMID: 29396015

Gerlach C*, Moseman EA*, Loughhead SM*, Alvarez D, Zwijnenburg AJ, Waanders L, Garg R, de la Torre, JC, von Andrian UH. The chemokine receptor CX3CR1 defines three antigen-experienced CD8 T cell subsets with distinct roles in immune surveillance and homeostasis. Immunity. 2016 Dec 20;45(6):1270-1284. PMID: 27939671

Rohr JC, Gerlach C, Kok L, Schumacher TN. Single cell behavior in T cell differentiation. Trends Immunol. 2014 Apr;35(4):170-7. PMID: 24657362

Gerlach C*, Rohr JC*, Perié L, van Rooij N, van Heijst JW, Velds A, Urbanus J, Naik SH, Jacobs H, Beltman JB, de Boer RJ, Schumacher TN. Heterogeneous differentiation patterns of individual CD8⁺ T cells. Science. 2013 May 3;340(6132):635-9. PMID: 23493421

Gerlach C, van Heijst JW, Schumacher TN. The descent of memory T cells. Ann N Y Acad Sci. 2011 Jan; 1217:139-53. PMID: 21251009

Gerlach C, van Heijst JW, Swart E, Sie D, Armstrong N, Kerkhoven RM, Zehn D, Bevan MJ, Schepers K, Schumacher TN. One naïve T cell, multiple fates in CD8⁺ T cell differentiation. J Exp Med. 2010 Jun 7;207(6):1235-46. PMID: 20479114

van Heijst JW, Gerlach C, Swart E, Sie D, Nunes-Alves C, Kerkhoven RM, Arens R, Correia-Neves M, Schepers K, Schumacher TN. Recruitment of antigen-specific CD8⁺ T cells in response to infection is markedly efficient. Science. 2009 Sep 4;325(5945):1265-9. PMID: 19729659

Here are some of our current and recent collaboration partners:

Group of Sara Gredmark Russ (Karolinska Institutet, Sweden)

https://ki.se/en/research/research-areas-centres-and-networks/research-groups/viruses-and-their-interactions-with-the-immune-system-sara-gredmark-russ-group

Group of Liv Eidsmo (Karolinska Institutet, Sweden)

https://ki.se/en/people/liv-eidsmo

Group of Nir Yosef (Weizmann Institute of Science, Israel)

https://www.weizmann.ac.il/immunology/yosef/

Group of Aaron Streets (UC Berkeley, USA) https://vcresearch.berkeley.edu/faculty/aaron-streets

Group of Randall Johnson (Karolinska Institutet, Sweden)

https://ki.se/en/research/research-areas-centres-and-networks/research-groups/effects-of-hypoxia-in-physiological-and-pathological-contexts-hypoxia-inducible-factors-hif-randall-johnsons-group#tab-start

Group of Soren Degn (Aarhus University, Denmark)

https://degnlab.au.dk/

Group of Karin Larsson (Karolinska Institutet, Sweden)

https://ki.se/en/people/karin-larsson

Group of Ulrich von Andrian (Harverd Medical School, USA)

https://vonandrian.hms.harvard.edu/people/ulrich-von-andrian

Center for Cellular Cancer Therapy (C3T).

Consortium focused on education, networking and recruitment of postdocs and junior PIs to expand competence and create a multidisciplinary environment for innovative adoptive cell therapies. Funded by a Swedish Research Council initiative for Centers of Excellence.

Prof. Carmen Gerlach

Head of Research Group | Tailored T-cell diversity

Email: carmen.gerlach@lit.eu