CD4+ T cell responses to the Plasmodium falciparum erythrocyte membrane protein 1 in children with mild malaria.
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.
KEMRI-Wellcome Trust Collaborative Programme, Centre for Geographic Medicine Coast, 80108 Kilifi, Kenya;
Evelyn N
EN
Gitau
James
J
Tuju
Henry
H
Karanja
Liz
L
Stevenson
Pilar
P
Requena
Eva
E
Kimani
Ally
A
Olotu
Domtila
D
Kimani
Kevin
K
Marsh
Peter
P
Bull
Britta C
BC
Urban
D000913:Antibodies, Protozoan / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007630:Kenya; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C508598:IL4 protein, human; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D015847:Interleukin-4; D007371:Interferon-gamma