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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.

Original publication

DOI

10.4049/jimmunol.1200547

Type

Journal article

Journal

J Immunol

Publication Date

15/02/2014

Volume

192

Pages

1753 - 1761

Keywords

Antibodies, Protozoan, Antigens, Protozoan, CD4-Positive T-Lymphocytes, Child, Child, Preschool, Cohort Studies, Erythrocytes, Female, Humans, Interferon-gamma, Interleukin-4, Kenya, Malaria, Falciparum, Male, Molecular Sequence Data, Plasmodium falciparum, Protein Structure, Tertiary, Protozoan Proteins