Blood and Beyond: improving properties of human virus-specific CD8+ T cells for adoptive immunotherapy. (LSBR 1136)
Project leader: Prof. Dr. René A.W. van Lier, Dept. of Hematopoiesis, Adaptive Immunity Lab, Sanquin Research, Amsterdam
Postdoc: Pleun Hombrink, PhD (Sept. 2012 – Sept. 2015)
Technician: Giso Brasser (Jun. 2013 – Jun. 2015)
T cells are important for our immune defense against pathogens and tumors. Whereas a fraction of T cells continuously circulates through the body, other populations take up permanent residency in organs such as lung, skin and gut. Recent work from our lab has revealed part of the molecular mechanism by showing that the related transcriptional repressors BLIMP-1 and HOBIT play a non-redundant role in inducing tissue residency of murine lymphocytes (Mackay et al., Science, 2016).
The current study was performed to increase our knowledge of resident T cells as they reside in the human lung. Three important conclusions can be drawn from our endeavors. First, by studying the expression of (immune-related) genes it became clear that the human lung contains different sets of tissue-residing T cells that can be separated into parenchymal and epithelial carrier cells. These cells are in an alerted state, which is not induced by standard effector function-inducing transcription factors but rather by a specific cell surface receptor that responds to signals coming from the tissue environment. Second, we found that not only for influenza virus but also for another respiratory virus, RSV, reactive T cells preferentially localize in the epithelial barrier, which appears to be a very adapted position when it comes to coping with incoming pathogens. Finally, we found novel ways to induce long-term expansion of tissue-resident T cells by using a newly developed culture medium. These studies have provided a basis for further studies in which (1) not only gene expression, but also protein expression will be addressed in a non-biased fashion, (2) resident T cells will be compared with tumor-infiltrating T cells and (3) the improved culture conditions will be used to address whether representative expansion of T cells can be achieved with preservation of function.