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Tissue dimensionality influences the functional response of cytotoxic T lymphocyte-mediated killing of targets

Gadhamsetty, Saikrishna, Maree, Athanasius F. M., de Boer, Rob J. and Beltman, Joost B. 2017. Tissue dimensionality influences the functional response of cytotoxic T lymphocyte-mediated killing of targets. Frontiers in Immunology 7 , 668. 10.3389/fimmu.2016.00668

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Cytotoxic T lymphocyte (CTL)-mediated killing of virus infections and tumors occurs over a wide range of conditions. The spatial environments in which CTLs encounter target cells vary from narrow vessels, to two-dimensional epithelial tissues, to densely populated 3-dimensional (3D) T cell areas within lymphoid tissues. How such spatial environments alter the functional response of CTL-mediated killing, i.e., how the killing efficiency depends on cell densities, is unclear. In this study, we perform cellular Potts model simulations in different spatial configurations to investigate how the dimensionality of the space affects the functional response of CTL-mediated killing. Irrespective of the spatial configuration, the function with separate saturation constants for CTL and for target cell densities that we previously proposed can in all cases describe the response, demonstrating its generality. However, the tissue dimensionality determines at which cell densities the killing rate starts to saturate. We show that saturation in a fully 3D environment is stronger than in a “flat” 3D environment, which is largely due to accompanying differences in the CTL–target encounter rates.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Frontiers Media
ISSN: 1664-3224
Date of First Compliant Deposit: 28 February 2019
Date of Acceptance: 19 December 2016
Last Modified: 26 Mar 2020 17:15

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