NDLI: In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages

Content Provider	PubMed Central
Author	Cockburn, Ian A. Amino, Rogerio Kelemen, Reka K. Kuo, Scot C. Tse, Sze-wah Radtke, Andrea Laura, Mac-daniel Ganusov, Vitaly V. Zavala, Fidel Ménard, Robert
Abstract	CD8+ T cells are specialized cells of the adaptive immune system capable of finding and eliminating pathogen-infected cells. To date it has not been possible to observe the destruction of any pathogen by CD8+ T cells in vivo. Here we demonstrate a technique for imaging the killing of liver-stage malaria parasites by CD8+ T cells bearing a transgenic T cell receptor specific for a parasite epitope. We report several features that have not been described by in vitro analysis of the process, chiefly the formation of large clusters of effector CD8+ T cells around infected hepatocytes. The formation of clusters requires antigen-specific CD8+ T cells and signaling by G protein-coupled receptors, although CD8+ T cells of unrelated specificity are also recruited to clusters. By combining mathematical modeling and data analysis, we suggest that formation of clusters is mainly driven by enhanced recruitment of T cells into larger clusters. We further show various death phenotypes of the parasite, which typically follow prolonged interactions between infected hepatocytes and CD8+ T cells. These findings stress the need for intravital imaging for dissecting the fine mechanisms of pathogen recognition and killing by CD8+ T cells.
Related Links	http://dx.doi.org/10.1073/pnas.1303858110
Ending Page	9095
Page Count	6
Starting Page	9090
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	22
Volume Number	110
Language	English
Publisher	National Academy of Sciences
Publisher Date	2013-05-28
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages.

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