CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria.
To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.
Lei Shong
LS
Lau
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.
Daniel
D
Fernandez-Ruiz
The School of Botany, University of Melbourne, Parkville, Victoria, Australia.
Vanessa
V
Mollard
The School of Botany, University of Melbourne, Parkville, Victoria, Australia.
Angelika
A
Sturm
The QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Michelle A
MA
Neller
The School of Botany, University of Melbourne, Parkville, Victoria, Australia.
Anton
A
Cozijnsen
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.
Julia L
JL
Gregory
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.
Gayle M
GM
Davey
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.
Claerwen M
CM
Jones
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.
Yi-Hsuan
YH
Lin
The QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Ashraful
A
Haque
The QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Christian R
CR
Engwerda
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Macfarlane Burnet Institute for Medical Research & Public Health, Melbourne, Victoria, Australia.
Catherine Q
CQ
Nie
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Diana S
DS
Hansen
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Kenneth M
KM
Murphy
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Anthony T
AT
Papenfuss
The QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, Wales, United Kingdom.
John J
JJ
Miles
The QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Scott R
SR
Burrows
School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
Tania
T
de Koning-Ward
The School of Botany, University of Melbourne, Parkville, Victoria, Australia.
Geoffrey I
GI
McFadden
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia.
Francis R
FR
Carbone
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia; Macfarlane Burnet Institute for Medical Research & Public Health, Melbourne, Victoria, Australia; Monash University, Clayton, Victoria, Australia.
Brendan S
BS
Crabb
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, Victoria, Australia; The ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Australia.
William R
WR
Heath
D019264:Adoptive Transfer; D000818:Animals; D000852:Anopheles; D001769:Blood / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D007117:Immunization, Secondary / Q000379:methods*; D008018:Life Cycle Stages / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008288:Malaria / Q000097:blood / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010962:Plasmodium berghei / Q000254:growth & development / Q000276:immunology*; D016788:Plasmodium chabaudi; D010967:Plasmodium yoelii; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D034101:Sporozoites / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell