title: In vitro cell-mediated immune responses to Plasmodium falciparum schizont antigens in adults from a malaria endemic area: CD8+ T lymphocytes inhibit the response of low responder individuals.
abstract: Plasmodium falciparum schizont extract and purified protein derivative were used to stimulate peripheral blood mononuclear cells obtained from healthy aparasitemic Gabonese individuals with lifelong exposure to malaria infection and non-Gabonese control subjects who have had had no clinical malaria. In vitro lymphoproliferation was measured by uptake of tritiated thymidine, while production of interleukin-2, interferon-gamma, and soluble CD8+ were measured by immunoenzymatic assays. Enumeration of interferon-gamma-producing cells was done using a modified immunoenzyme spot assay. Twenty-eight percent of Gabonese subjects were determined to be low responders in the lymphoproliferative assay, with a tritiated thymidine uptake of less than 6000 c.p.m. The proportions of T cell subsets and the kinetics of the proliferative response were similar in the low and the high responders. Removal of CD8+ T cells from mononuclear cells of low responders or culture of purified CD4+ T cells from the same individuals resulted in a 7-fold increase in the proliferative response to the schizont antigen but not to purified protein derivative (PPD). A similar increase in the proliferative response was seen in the low but not the high responder mononuclear cell cultures stimulated with the schizont antigen in the presence of exogenous interleukin 2 (IL-2) or in the presence of anti-HLA-DQ antibody. Low responder mononuclear cell cultures stimulated with schizont antigen but not PPD produced 3-fold less IL-2, 14-fold less interferon-gamma (IFN-gamma), and 3-fold more soluble CD8 than high responder mononuclear cell cultures. Removal of CD8+ T cells from low responder mononuclear cells resulted in a 2-fold increase in IL-2 production and a 4-fold increase in IFN-gamma production in response to schizont antigen. High responder mononuclear cells stimulated with schizont antigen contained four times as much IFN-gamma-producing cells as low responder cultures, with each IFN-gamma-producing cell producing three times the amount of IFN-gamma as that produced by an IFN-gamma-producing cell in low responder cultures. Removal of CD8+ T cells from low responder mononuclear cells led to a significant increase in the amount of IFN-gamma produced at the single cell level in response to schizont antigen stimulation. In such cultures, the amount of IFN-gamma produced by a single cell was similar between high and low responders. We conclude that in certain individuals, T cell responses to schizont antigen are actively down-regulated by activated schizont-specific CD8+ suppressor T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
authors: Department of Immunoparasitology, International Medical Research Center (CIRMF), Franceville, Gabon.
authors: R N
authors: RN
authors: Mshana
authors: S
authors: S
authors: McLean
authors: J
authors: J
authors: Boulandi
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D005260:Female; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2; D007371:Interferon-gamma