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CD4+ T cell responses to the Plasmodium falciparum erythrocyte membrane protein 1 in children with mild malaria.

Abstract
The immune response against the variant surface Ag Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against malaria. We have investigated the development and maintenance of CD4(+) T cell responses to a small semiconserved area of the Duffy binding-like domain (DBL)α-domain of PfEMP1, the DBLα-tag. Young children were followed up longitudinally, and parasites and PBMCs were isolated from 35 patients presenting with an acute case of uncomplicated malaria. The DBLα-tag from the PfEMP1 dominantly expressed by the homologous parasite isolate was cloned and expressed as recombinant protein. The recombinant DBLα-tag was used to activate PBMCs collected from each acute episode and from an annual cross-sectional survey performed after the acute malaria episode. In this article, we report that CD4(+) T cell responses to the homologous DBLα-tag were induced in 75% of the children at the time of the acute episode and in 62% of the children at the following cross-sectional survey on average 235 d later. Furthermore, children who had induced DBLα-tag-specific CD4(+)IL-4(+) T cells at the acute episode remained episode free for longer than children who induced other types of CD4(+) T cell responses. These results suggest that a wide range of DBLα-tag-specific CD4(+) T cell responses were induced in children with mild malaria and, in the case of CD4(+)IL-4(+) T cell responses, were associated with protection from clinical episodes.
AuthorsEvelyn N Gitau, James Tuju, Henry Karanja, Liz Stevenson, Pilar Requena, Eva Kimani, Ally Olotu, Domtila Kimani, Kevin Marsh, Peter Bull, Britta C Urban
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 192 Issue 4 Pg. 1753-61 (Feb 15 2014) ISSN: 1550-6606 [Electronic] United States
PMID24453249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • IL4 protein, human
  • Protozoan Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • Interleukin-4
  • Interferon-gamma
Topics
  • Antibodies, Protozoan (immunology)
  • Antigens, Protozoan (immunology)
  • CD4-Positive T-Lymphocytes (immunology)
  • Child
  • Child, Preschool
  • Cohort Studies
  • Erythrocytes (immunology, parasitology)
  • Female
  • Humans
  • Interferon-gamma (metabolism)
  • Interleukin-4 (metabolism)
  • Kenya
  • Malaria, Falciparum (immunology)
  • Male
  • Molecular Sequence Data
  • Plasmodium falciparum (immunology)
  • Protein Structure, Tertiary
  • Protozoan Proteins (immunology)

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