Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8α+ dendritic cells
Lundie, Rachel J., de Koning-Ward, Tania, Davey, Gayle M., Nie, Catherine Q., Hansen, Diana S., Lau, Lei Shong, Mintern, Justine D., Belz, Gabrielle T., Schofield, Louis, Carbone, Frances R., Villadangos, Jose A., Crabb, Brendan S. and Heath, William R. 2008, Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8α+ dendritic cells, Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 38, pp. 14509-14514, doi: 10.1073/pnas.0806727105.
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Title
Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8α+ dendritic cells
Proceedings of the National Academy of Sciences of the United States of America
Volume number
105
Issue number
38
Start page
14509
End page
14514
Total pages
6
Publisher
National Academy of Sciences
Place of publication
Washington, D.C.
Publication date
2008-09
ISSN
0027-8424 1091-6490
Summary
Although CD8+ T cells do not contribute to protection against the blood stage of Plasmodium infection, there is mounting evidence that they are principal mediators of murine experimental cerebral malaria (ECM). At present, there is no direct evidence that the CD8+ T cells mediating ECM are parasite-specific or, for that matter, whether parasite-specific CD8+ T cells are generated in response to blood-stage infection. To resolve this and to define the cellular requirements for such priming, we generated transgenic P. berghei parasites expressing model T cell epitopes. This approach was necessary as MHC class I-restricted antigens to blood-stage infection have not been defined. Here, we show that blood-stage infection leads to parasite-specific CD8+ and CD4+ T cell responses. Furthermore, we show that P. berghei-expressed antigens are cross-presented by the CD8α+ subset of dendritic cells (DC), and that this induces pathogen-specific cytotoxic T lymphocytes (CTL) capable of lysing cells presenting antigens expressed by blood-stage parasites. Finally, using three different experimental approaches, we provide evidence that CTL specific for parasite-expressed antigens contribute to ECM.
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