Antigens released at schizont burst stimulate Plasmodium falciparum-specific CD4+ T cells from non-exposed donors: potential for cross-reactive memory T cells to cause disease.
In an individual experiencing the first attack of malaria, symptoms of disease can occur at very low parasitemia. T cells and cytokines have been implicated in the etiology of disease symptoms, and others and ourselves have shown that T cells from non-exposed individuals can be stimulated by malaria parasites. Here, we show that nine from 11 blood samples, naturally infected with malaria parasites, could stimulate proliferation of a malaria-specific T cell clone derived from a non-exposed donor. T cells were able to respond to infected blood at a parasitaemia as low as 0.000003% (comparable to the level at which individuals can first experience symptoms of malaria) and secrete cytokines implicated in pathology. Antigens capable of stimulating T cells are expressed throughout the blood stage, but are specifically released at the time of schizont rupture. While most TCR V beta genes are expressed during the T cell response of naive donors to malaria parasites, processing of parasite antigens is blocked by chloroquine and monensin, and activation of 36 of 41 malaria-specific clones tested was restricted by defined MHC class II allelic antigens, strongly suggesting that parasites do not act as mitogens nor as superantigens. The clones react to various commonly encountered pathogenic and non-pathogenic microbes. These data support the concept that activation of cross-reactive memory T cells by malaria parasites contributes to disease symptoms in individuals experiencing their first attack of malaria.
Currier
J
J
Malaria and Arbovirus Unit, Queensland Institute of Medical Research, Brisbane, Australia.
Beck
H P
HP
Currie
B
B
Good
M F
MF
D000293:Adolescent; D000328:Adult; D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000097:blood / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000209:etiology* / Q000276:immunology / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D013045:Species Specificity
D000953:Antigens, Protozoan