Cells of normal primed givers in vitro answer to the antigen to ovular soluble and synthetic peptíde MAP4 derived from triose-phosphate isomerase of the Schistosoma mansoni.
It has been well established that Schistosoma mansoni induces an initial CD4+ T-cell response. The early events in the immune response to schistosomiasis have been evaluated inmice but few studies have focused on the early response in humans, especially in regard to parasite antigens that are potential vaccine candidates. To study the early immune response in humans, we performed an in vitro assay mimicking the probable in vivo conditions. Naïve peripheral blood mononuclear cell (PBMCs) were exposed to S. mansoni soluble egg antigen (SEA) or a synthetic multiple antigen peptide containing B and T cell epitopes from Triose Phosphate Isomerase (MAP4) in a priming in vitro assay. Priming in vitro has been used recently as an important tool to reproduce in vitro the conditions of natural infection. Dendritic cells were used as antigen presenting cells. PBMCs from twelve healthy volunteers with no previous history of exposure to S. mansoni were stimulated by SEA or MAP4. Dendritic cells were generated, characterized and incubated in the presence or absence of antigen, and cultured with total PBMCs for seven days corresponding to a three day period ofnatural infection. Primed cells were collected and restimulated a further two times. At each step cytokine secretion was evaluated in the culture supernatant. The phenotypes of thelymphocyte subsets were determined after priming, first and second recall. Donor SEAprimed PBMCs developed a Th2-like response except for 2/12 donors who exhibited anatypical Th1-like response. In contrast to the effects of SEA stimulation, MAP4-primed cells developed a Th1-like response. Both antigens reproduced the effects previously observed invitro and in vivo in the murine model. The present results suggest that SEA and MAP4 sensitized dendritic cells are able to induce specific lymphocyte proliferation and clonalexpansion.
Advisor:Mitermayer Galvão dos Reis
School:Faculdades Oswaldo Cruz
Source Type:Master's Thesis
Keywords:Schistosoma mansoni Cytokines Immunity, Cellular Schistosomiasis In Vitro
Date of Publication:11/23/2007