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To fully perform their functions, T lymphocytes migrate within organs' parenchyma and interact with local cells. Infiltration of T lymphocytes within the central nervous system (CNS) is associated with numerous neurodegenerative disorders. Nevertheless, how these immune cells communicate and respond to neural cells remains unresolved. To investigate the behavior of T lymphocytes that reach the CNS, we have established an in vitro co-culture model and analyzed the spatiotemporal interactions between human activated CD8 + T lymphocytes and primary human astrocytes and neurons using time-lapse microscopy. By combining multiple variables extracted from individual CD8 + T cell tracking, we show that CD8 + T lymphocytes adopt a more motile and exploratory behavior upon interacting with astrocytes than with neurons. Pretreatment of astrocytes or neurons with IL-1β to mimic in vivo inflammation significantly increases CD8 + T lymphocyte motility. Using visual interpretation and analysis of numerical variables extracted from CD8 + T cell tracking, we identified four distinct CD8 + T lymphocyte behaviors: scanning, dancing, poking and round. IL-1β-pretreatment significantly increases the proportion of scanning CD8 + T lymphocytes, which are characterized by active exploration, and reduces the proportion of round CD8 + T lymphocytes, which are less active. Blocking MHC class I on astrocytes significantly diminishes the proportion of poking CD8 + T lymphocytes, which exhibit synapse-like interactions. Lastly, our co-culture time-lapse model is easily adaptable and sufficiently sensitive and powerful to characterize and quantify spatiotemporal interactions between human T lymphocytes and primary human cells in different conditions while preserving viability of fragile cells such as neurons and astrocytes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lemaître, Carmena Moratalla, Farzam-kia, Carpentier Solorio, Tastet, Cleret-Buhot, Guimond, Haddad and Arbour.)

The safe utilization of induced pluripotent stem cell (iPSC) derivatives in clinical use is attributed to the complete elimination of the risk of forming teratomas after transplantation. The extent by which such a risk exists in immune-competent hosts is mostly unknown. Here, using humanized mice reconstituted with fetal hematopoietic stem cells and autologous thymus tissue (bone-liver-thymus humanized mice [Hu-BLT]) or following the adoptive transfer of peripheral blood mononuclear cells(PBMCs) (Hu-AT), we evaluated the capacity of immune cells to prevent or eliminate teratomas derived from human iPSCs (hiPSCs). Our results showed that the injection of hiPSCs failed to form teratomas in Hu-AT mice reconstituted with allogeneic or autologous PBMCs or purified natural killer (NK) cells alone. However, teratomas were observed in Hu-AT mice reconstituted with autologous PBMCs depleted from NK cells. In line with these results, Hu-BLT, which do not have functional NK cells, could not prevent the growth of teratomas. Finally, we found that established teratomas were not targeted by NK cells and instead were efficiently rejected by allogeneic but not autologous T cells in Hu-AT mice. Overall, our findings suggest that autologous hiPSC-derived therapies are unlikely to form teratomas in the presence of NK cells., (Copyright © 2019 Benabdallah, Désaulniers-Langevin, Colas, Li, Rousseau, Guimond, Haddad and Beauséjour.)