Lundie, Rachel J., de Koning-Ward, Tania F., Davey, Gayle M., Nie, Catherine Q., Hansen, Diana S., Lau, Lei Shong, Mintern, Justine D., Belz, Gabrielle T., Schofield, Louis, Carbone, Francis 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 CD8 + dendritic cells. Proceedings of the National Academy of Sciences of the United States of America, 105 (38). pp. 14509-14514.

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Abstract

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.

Item ID:	35870
Item Type:	Article (Research - C1)
ISSN:	1091-6490
Keywords:	dendritic cells, malaria, antigen presentation, cytotoxic T lymphocyte, cerebral malaria
Funders:	National Health and Medical Research Council (NHMRC), Australian Postgraduate Award, Cooperative Research Centre for Vaccine Technology, Howard Hughes Medical Institute
Date Deposited:	31 Oct 2014 00:01
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50% 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 50%
SEO Codes:	97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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