Idiotypic network interactions involve an antigen-binding site which is associated with the variable region of the immunoglobulin molecule. The prediction is that both the antigen binding antibody and the anti- idiotypic antibody belong to the same family and that each can bind either an antigenic molecule or the immunoglobulin variable region. The T cell receptor is also dual in regard to the ability to bind antigen in the context of MHC Class II molecules or through an anti-clonotypic antibody. Our laboratories have studied these idiotype/anti-idiotype T cell interactions in human schistosomiasis and made the following observations. 1) T cells isolated from peripheral blood mononuclear cells of patients infected with Schistosoma mansoni are capable of responding in a lymphocyte proliferation assay to anti-SEA antibodies. 2) This observed 'anti-idiotypic' response could be defined by the nature of the idiotypes expressed on the anti-SEA antibodies. For example, anti-SEA antibodies collected from chronically infected intestinal patients were idiotypically different than anti-SEA antibodies recovered from hepatosplenic or acute patients based on competitive ELISA data generated with rabbit anti-SEA specific sera for each clinical group. 3) Furthermore, the anti-SEA antibodies from chronic intestinal patients were able to stimulate peripheral blood mononuclear cells from other intestinal patients as well as hepatosplenic patients. However, the anti-SEA antibodies from either acute or hepatosplenic patients were unable to stimulate proliferative responses in patients from any clinical form. 4) Finally, studies on CD4+ and CD8+ T cell populations from actively infected patients demonstrated that anti-SEA antibodies could stimulate these cells to proliferate and regulate granuloma formation. These findings were easily and repeatedly demonstrated in chronic intestinal patients. Hepatosplenic patients were unable to modulate their in vitro granuloma formation suggesting a failure of these stimulatory idiotypes to trigger regulation. Our studies have focussed on the description of the nature of idiotypy in schistosmoiasis patients and the functional role of network interactions in regulation of the host/parasite response. We now propose to study the molecular mechanisms of the idiotype/anti- idiotypic interactions in human schistosomiasis by studying the gene and protein structures of the initiating antigen/antibody interactions and the idiotypic/TCR or other ligands on the CD4+ and CD8+ T cells that are involved in the induction of proliferation and regulation of granuloma formation.
|Vago, A R; Macedo, A M; Adad, S J et al. (1996) PCR detection of Trypanosoma cruzi DNA in oesophageal tissues of patients with chronic digestive Chagas' disease. Lancet 348:891-2|