A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria

Amante, Fiona H., Stanley, Amanda C., Randall, Louise M., Zhou, Yonghong, Haque, Ashraful, McSweeney, Karli, Waters, Andrew P., Janse, Chris J., Good, Michael F., Hill, Geoff R. and Engwerda, Christian R. (2007) A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. American Journal of Pathology, 171 2: 548-559. doi:10.2353/ajpath.2007.061033


Author Amante, Fiona H.
Stanley, Amanda C.
Randall, Louise M.
Zhou, Yonghong
Haque, Ashraful
McSweeney, Karli
Waters, Andrew P.
Janse, Chris J.
Good, Michael F.
Hill, Geoff R.
Engwerda, Christian R.
Title A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria
Journal name American Journal of Pathology   Check publisher's open access policy
ISSN 0002-9440
Publication date 2007-08
Sub-type Article (original research)
DOI 10.2353/ajpath.2007.061033
Volume 171
Issue 2
Start page 548
End page 559
Total pages 12
Place of publication Birmingham, A. L.
Publisher American Society for Investigative Pathology
Collection year 2008
Language eng
Subject C1
321010 Infectious Diseases
730102 Immune system and allergy
Abstract Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection that is responsible for a significant number of deaths in children and nonimmune adults. A failure to control blood parasitemia and subsequent sequestration of parasites to brain microvasculature are thought to be key events in many CM cases. Here, we show for the first time, to our knowledge, that CD4(+)CD25(+)Foxp3(+) natural regulatory T (Treg) cells contribute to pathogenesis by modulating immune responses in P. berghei ANKA (PbA)-infected mice. Depletion of Treg cells with anti-CD25 monoclonal antibody protected mice from experimental CM. The accumulation of parasites in the vasculature and brain was reduced in these animals, resulting in significantly lower parasite burdens compared with control animals. Mice lacking Treg cells had increased numbers of activated CD4(+) and CD8(+) T cells in the spleen and lymph nodes, but CD8+ T-cell recruitment to the brain was selectively reduced in these mice. importantly, a non-Treg-cell source of interleukin-10 was critical in preventing experimental CM. Finally, we show that therapeutic administration of anti-CD25 monoclonal antibody, even when blood parasitemia is established, can prevent disease, confirming a critical and paradoxical role for Treg cells in experimental CM pathogenesis.
Keyword Pathology
Tumor-necrosis-factor
Central-nervous-system
Nitric-oxide Synthase
Plasmodium-falciparum
Monoclonal-antibody
Interferon-gamma
Clinical-features
African Children
Dendritic Cells
Blood Stages
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2008 Higher Education Research Data Collection
School of Public Health Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 110 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 18 Feb 2008, 14:35:36 EST