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Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8α+ dendritic cells

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posted on 2008-09-01, 00:00 authored by R Lundie, Tania De Koning-WardTania De Koning-Ward, G Davey, C Nie, D Hansen, L Lau, J Mintern, G Belz, L Schofield, F Carbone, J Villadangos, B Crabb, W Heath
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.

History

Journal

Proceedings of the National Academy of Sciences of the United States of America

Volume

105

Pagination

14509 - 14514

Location

Washington, D.C.

Open access

  • Yes

ISSN

0027-8424

eISSN

1091-6490

Language

eng

Publication classification

C1 Refereed article in a scholarly journal; C Journal article

Copyright notice

2008, National Academy of Sciences