Blood-stage Plasmodium infection induces CD+ T lymphocytes to parasite-expressed antigens, largely regulated by CDα+ 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 CD+ T lymphocytes to parasite-expressed antigens, largely regulated by CDα+ dendritic cells, Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 38, pp. 14509-14514.


Title Blood-stage Plasmodium infection induces CD+ T lymphocytes to parasite-expressed antigens, largely regulated by CDα+ dendritic cells
Author(s) 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.
Heath, William R.
Journal name 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
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.
Language eng
Field of Research 110707 Innate Immunity
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
HERDC collection year 2008
Copyright notice ©2008, National Academy of Sciences
Persistent URL http://hdl.handle.net/10536/DRO/DU:30017528

Document type: Journal Article
Collection: School of Medicine
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