Journal article
Lethal giant larvae-1 deficiency enhances the CD8 effector T-cell response to antigen challenge in vivo
KM Ramsbottom, F Sacirbegovic, ED Hawkins, A Kallies, GT Belz, V Van Ham, NM Haynes, MJ Durrant, PO Humbert, SM Russell, J Oliaro
Immunology and Cell Biology | Published : 2016
DOI: 10.1038/icb.2015.82
Abstract
Lethal giant larvae-1 (Lgl-1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl-1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl-1 in T cells, we generated chimeric mice with a hematopoietic system deficient for Lgl-1. Lgl-1 deficiency did not impair the activation or function of peripheral CD8+ T cells in response to antigen presentation in vitro, but did skew effector and memory T-cell differentiation. When challenged with antigen-expressing virus or tumor, Lgl-1-deficient mice displayed altered T-cell responses. This manifested in a stronger antiviral and antitumor effector CD8+..
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Funding Acknowledgements
We thank Valera Vasioukhin (Fred Hutchinson Cancer Research Center) for the C57BL/6 Lgl-1-deficient mice and S. Williams for colony management. This work was supported by grants and fellowships from the National Health and Medical Research Council, Australian Research Council and Human Frontier Science Program.