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© Research
Publication : Proceedings of the National Academy of Sciences of the United States of America

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 14 May 2013

Cockburn IA, Amino R, Kelemen RK, Kuo SC, Tse SW, Radtke A, Mac-Daniel L, Ganusov VV, Zavala F, Ménard R

Link to Pubmed [PMID] – 23674673

Proc. Natl. Acad. Sci. U.S.A. 2013 May;110(22):9090-5

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.

http://www.ncbi.nlm.nih.gov/pubmed/23674673