2013
DOI: 10.1073/pnas.1303858110
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In vivo imaging of CD8+T cell-mediated elimination of malaria liver stages

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 format… Show more

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Cited by 125 publications
(309 citation statements)
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“…To our knowledge, this study presents the first direct evidence of chemoattraction toward regions of interest of effector T cells within a peripheral tissue. Prior studies in other peripheral tissues did not detect directional migration (16,17), or postulated its occurrence on the basis of indirect observations (7,15). It may be interesting to reanalyze such existing data by the strategies used here, to evaluate whether similar subtle migration behaviors are hidden in timelapse imaging data sets.…”
Section: Discussionmentioning
confidence: 85%
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“…To our knowledge, this study presents the first direct evidence of chemoattraction toward regions of interest of effector T cells within a peripheral tissue. Prior studies in other peripheral tissues did not detect directional migration (16,17), or postulated its occurrence on the basis of indirect observations (7,15). It may be interesting to reanalyze such existing data by the strategies used here, to evaluate whether similar subtle migration behaviors are hidden in timelapse imaging data sets.…”
Section: Discussionmentioning
confidence: 85%
“…infection foci secrete chemokines upon target encounter, thereby reinforcing the attraction of yet more effector T cells (in a similar fashion, specific CD8 + T cells clustering around malaria-infected hepatocytes were proposed to locally secrete factors that result in the recruitment of additional effector T cells (15).…”
Section: Figure 5 Directed Migration Of Effector T Cells Is Lost Upomentioning
confidence: 97%
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“…For example, we have previously shown that contact-dependent killing of infected hepatocytes by CD8 + T cells is a major effector mechanism in BALB/c mice vaccinated with genetically attenuated spz (18). More recently, it has been proposed that CD8 + T cells that interact with infected hepatocytes can recruit both parasite-specific and bystander CD8 + T cells to the proximity of infected hepatocytes, although only parasite-specific CD8 + T cells appear to be involved in killing the infected hepatocytes (30,31).…”
Section: Itv-induced Cd8 + T Cell Responses Are Cytotoxic To Ls Parasmentioning
confidence: 99%
“…2016. 46: 885-896 Plasmodium-specific CD8 + T cells [22,57] The TAP-dependent pathway in WT mice may provide a richer peptide pool with higher affinity MHC I:peptide interactions for CD8 + T cells, hence assuring a higher number of more proficient CD8 + T E cells. Conversely, the TAP-independent pathway is less efficient owing to reduced concentration of MHC I molecules [60] and hence a slower egress of MHC I:peptide complexes.…”
Section: Discussionmentioning
confidence: 99%