Characterization of regulatory T-cell responses in humans induced by the P. Falciparum blood stage antigen Pf155/RESA

Abstract

T-cells have a major role both as helper cells for efficient antibody production and as inducers and effector cells in antibody-independent malaria immunity. Thus, antigens to be included into a subunit vaccine must contain T-cell epitopes to become effectively immunogenic. The P. falciparum blood stage vaccine antigen Pf155/RESA has been shown to contain T-helper epitopes inducing T-dependent anti-malarial antibodies in vitro. We have also shown that synthetic peptides representing sequences from the amino-acid repeat regions of Pf155/RESA stimulate T-cells from P. falciparum primed donors to proliferate, to release IFN-gamma and/or IL-4. In individual donors there was no correlation between these different activities. Rather, they were frequently negatively associated. However, IL-4 secretion could be induced in T-cells from donors who had elevated concentrations of serum antibodies to the same peptide as used for T-cell activation. Taken together the results support the occurrence of malaria-specific CD4+ T-cell subsets (e.g. TH1 and TH2) in humans similar to what has been found in mice and suggest the involvement of TH2-type helper cells in the induction of some important P. falciparum specific antibodies. CD4+ T-cells recognize the antigen in the context of MHC class II molecules. However, in human outbred populations no consistent MHC restrictions of anti-Pf155/RESA immune responses could be demonstrated. This is not surprising in view of the extensive polymorphism of the HLA system. Neither were there any obvious MHC class II restrictions seen when antibody- and t-cell responses were measured in naturally primed monozygotic twins.(ABSTRACT TRUNCATED AT 250 WORDS)