General
Guest lecture at Sanquin Amsterdamby Carmen Gerlach, research group leader at the Department of Medicine Solna of the Karolinska Institute in Stockholm.
About Carmen Gerlach:
Carmen Gerlach is research group leader at the Department of Medicine Solna of the Karolinska Institute in Stockholm. During her PhD in Ton Schumacher’s lab at the Netherlands Cancer Institute (2005-2011) she developed with a few colleagues a cellular barcoding technology that allows in vivo tracking and fate mapping of single naive T cells. Using this technology, they established that while virtually all naive CD8 T cells give rise to both effector and memory cell progeny (Gerlach et al., J.Exp. Med. 2010), individual naive T cells nevertheless mount very distinct immune responses to facilitate robustness of the overall response (Gerlach et al., Science 2013). During her postdoc in Ulrich von Andrian’s lab at Harvard Medical School in Boston (2011-2017), she studied the memory CD8 T cell response in more detail, which led to the delineation of a novel subset, named ‘peripheral memory cells (Tpm)’ that has unique migratory, homeostatic and functional properties (Gerlach et al., Immunity 2016). To gain a better understanding of the computational aspects involved in the analysis of (immune) cells with the current high-dimensional single-cell technologies, she spent 8 months as visiting scholar in Nir Yosef’s lab at the University of California in Berkeley, USA (2017) before starting as Assistant Professor at the Karolinska Institute in Stockholm. The research in her group aims to unravel basic principles and mechanisms underlying the generation, maintenance, and consequences of the diversity within CD8+ T cell responses.
Title talk: Connecting human and murine T cell diversification
When naïve T cells are activated and clonally expand, the progeny differentiates into a heterogeneous population of functionally distinct states or ‘subsets’. The differentiation state of a T cells is indicative of its functional and migratory properties, and T cell differentiation states are furthermore linked to clinical outcome, for example, after infection, adoptive T cell therapy or transplantation.
It is, however, difficult to translate T cell behavior (i.e. functional and migration properties) across species, since the cell surface markers that separate distinct differentiation states are largely different for murine and human CD4+ and CD8+ T cells. The lack of common markers to define the same T cell differentiation states in both species makes it difficult to link observational data from human T cell subsets to mechanistic mouse studies, and to employ knowledge on the generation and lineage relationships form murine T cells subsets to improve, for example, human vaccines. Furthermore, recent high-resolution analysis has revealed a range of functionally distinct T cell states that go beyond the division into the classical TSCM, TCM, TEM and TEMRA. Consequently, there is a need for cross-species, broadly applicable and easily measurable markers that can accurately reflect the graded T cell states along the differentiation state continuum to capture the breath of functional states beyond the categorical division into TSCM, TCM, TEM and TEMRA.
With the goal to provide a practical tool to facilitate optimal two-way crosstalk between human and mouse settings, we set out to identify T cell differentiation markers that capture the continuous nature of T cell differentiation and identify fine-graded differentiation states with comparable functional properties in both human and murine CD8+ T cells. I will be showing the results of this study.
Host: Monika Wolkers