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

Ian A. Cockburn, Rogerio Amino, Reka K. Kelemen, Scot C Kuo, Sze Wah Tse, Andrea Radtke, Laura Mac-Daniel, Vitaly V. Ganusov, Fidel P Zavala, Robert Ménard

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)9090-9095
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number22
DOIs
StatePublished - May 28 2013

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Malaria
T-Lymphocytes
Liver
Parasites
Hepatocytes
T-Cell Antigen Receptor Specificity
CD8 Antigens
G-Protein-Coupled Receptors
T-Cell Antigen Receptor
Epitopes
Immune System
Phenotype

Keywords

  • Immunity
  • Lymphocytes
  • Plasmodium

ASJC Scopus subject areas

  • General

Cite this

In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages. / Cockburn, Ian A.; Amino, Rogerio; Kelemen, Reka K.; Kuo, Scot C; Tse, Sze Wah; Radtke, Andrea; Mac-Daniel, Laura; Ganusov, Vitaly V.; Zavala, Fidel P; Ménard, Robert.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 22, 28.05.2013, p. 9090-9095.

Research output: Contribution to journalArticle

Cockburn, Ian A. ; Amino, Rogerio ; Kelemen, Reka K. ; Kuo, Scot C ; Tse, Sze Wah ; Radtke, Andrea ; Mac-Daniel, Laura ; Ganusov, Vitaly V. ; Zavala, Fidel P ; Ménard, Robert. / In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 22. pp. 9090-9095.
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