期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 22, 页码 9090-9095出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1303858110
关键词
Plasmodium; immunity; lymphocytes
资金
- French Government's Investissement d'Avenir program [ANR-10-LABX-62-IBEID]
- French National Research Agency [ANR-10-JCJC-1302-PlasmoPEP]
- National Institutes of Health [AI44375]
- European Molecular Biology Organization short-term fellowship
- Bloomberg Family Foundation
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.
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