Abstract
T cells play critical roles in controlling hepatotropic viral infections and liver tumors. The protective capacity of these cells is mediated by antigen-experienced effector cells and depends on their ability to migrate to and traffic within the liver, recognize pathogen- or tumor-derived antigens, get activated and deploy effector functions.
While some of the rules that characterize T cell behavior in the healthy and cancerous antigen-expressing liver have been characterized at the population level, we have only limited knowledge of the precise dynamics of T cell interactions with different kinds of liver cells at the single-cell level. Here, we describe in detail an intravital microscopy technique that allows the analysis of T cell dynamic behavior in the liver of anesthetized mice at high spatial and temporal resolution. A detailed understanding of the spatiotemporal dynamics of T cells within the liver is important for the rational design of targeted immunotherapeutic approaches for chronic liver infections and tumors.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Germain RN, Robey EA, Cahalan MD (2012) A decade of imaging cellular motility and interaction dynamics in the immune system. Science 336(6089):1676–1681. doi:10.1126/science.1221063
Murooka TT, Mempel TR (2012) Multiphoton intravital microscopy to study lymphocyte motility in lymph nodes. Methods Mol Biol 757:247–257. doi:10.1007/978-1-61779-166-6_16
Guidotti LG, Inverso D, Sironi L et al (2015) Immunosurveillance of the liver by intravascular effector CD8(+) T cells. Cell 161(3):486–500. doi:10.1016/j.cell.2015.03.005
Iannacone M (2015) Hepatic effector CD8(+) T-cell dynamics. Cell Mol Immunol 12(3):269–272. doi:10.1038/cmi.2014.78
Inverso D, Iannacone M (2015) Spatiotemporal dynamics of effector CD8+ T cell responses within the liver. J Leukoc Biol 99(1):51–55. doi:10.1189/jlb.4MR0415-150R
Pircher H, Bürki K, Lang R et al (1989) Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342(6249):559–561. doi:10.1038/342559a0
Hogquist KA, Jameson SC, Heath WR et al (1994) T cell receptor antagonist peptides induce positive selection. Cell 76(1):17–27. doi:10.1016/0092-8674(94)90169-4
Isogawa M, Chung J, Murata Y et al (2013) CD40 activation rescues antiviral CD8+ T cells from PD-1-mediated exhaustion. PLoS Pathog 9(7):e1003490. doi:10.1371/journal.ppat.1003490
Iannacone M, Sitia G, Isogawa M et al (2005) Platelets mediate cytotoxic T lymphocyte-induced liver damage. Nat Med 11(11):1167–1169. doi:10.1038/nm1317
Manjunath N, Shankar P, Wan J et al (2001) Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes. J Clin Invest 108(6):871–878. doi:10.1172/JCI13296
Guidotti LG, Matzke B, Schaller H, Chisari FV (1995) High-level hepatitis B virus replication in transgenic mice. J Virol 69(10):6158–6169
Iannacone M, Sitia G, Narvaiza I et al (2007) Antiplatelet drug therapy moderates immune-mediated liver disease and inhibits viral clearance in mice infected with a replication-deficient adenovirus. Clin Vaccine Immunol 14(11):1532–1535. doi:10.1128/CVI.00298-07
Sitia G, Iannacone M, Aiolfi R et al (2011) Kupffer cells hasten resolution of liver immunopathology in mouse models of viral hepatitis. PLoS Pathog 7(6):e1002061. doi:10.1371/journal.ppat.1002061
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media New York
About this protocol
Cite this protocol
Benechet, A.P., Ganzer, L., Iannacone, M. (2017). Intravital Microscopy Analysis of Hepatic T Cell Dynamics. In: Lugli, E. (eds) T-Cell Differentiation. Methods in Molecular Biology, vol 1514. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6548-9_4
Download citation
DOI: https://doi.org/10.1007/978-1-4939-6548-9_4
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-6546-5
Online ISBN: 978-1-4939-6548-9
eBook Packages: Springer Protocols