Anti-Idiotypic T cells in human Schistosomiasis

Abstract

We have developed an in vitro model of granuloma formation for the purpose of studying the immunological components of granulomatous hypersensitivity in patients infected with S. mansoni. Our previous studies have shown that 1) granulomatous hypersensitivity can be studied by examining the cellular reactivity manifested as multiple cell layers surrounding antigen-conjugated polyacrylamide beads; and 2) this reactivity is a CD4 T cell dependent, macrophage dependent, B cell independent response which is antigenically specific for parasite egg antigens. We report here on idiotype - anti-idiotype receptor interactions involved in the regulation of granulomatous hypersensitivity in patients and former patients infected with S. mansoni. Five human monoclonal antibodies specific for parasite egg antigens were used to activate CD4 and CD8 T cell subsets. These activated anti-idiotypic T cells were then assayed for regulatory effector functions in an autologous in vitro granuloma model.

Regulation of Immunity to Parasites by T Cells and T Cell-Derived Cytokines

“…In human schisto somiasis, idiotypes on antiegg antibodies from asymptomatic, chronically infected individuals induce proliferative responses in their own and often in other individuals' T cells, while similar preparations of anti egg anti bodies from patients with the hepatosplenic form of the disease fail to do so (130). Further evidence for a regulatory function for this antiidiotypic response comes from studies in which T cells (from chronically infected subjects) prestimulated with homologous idiotype were shown to suppress in vitro granuloma formation induced by autologous peripheral blood mononuclear cells from the same patients (131). A similar scenario has been described in humans infected with T. cruzi (Chagas' disease), where patients with cardiac forms of the disease express stronger antiidiotypic T cell responses against idiotypes on antiepimastigote antibodies than do individuals with asymptomatic (indeterminate) infections (132).…”

Immunologic Basis of Disease and Disease Regulaiton in Schistosomiasis

“…An idiotypically connected immunoregulatory circuit involving CRI expressed on anti-SEA antibodies and a series of anti-idiotypic T cells has been described [84]. The presence of autologous anti-idiotypic T cells reactive to anti-SEA antibodies from intestinal patients has been reported.…”

Granulomatous hypersensitivity to Schistosoma mansoni EGG antigens in human schistosomiasis. IV. A role for prostaglandin‐induced inhibition of in vitro granuloma formation

“…It has been demonstrated previously that the chronic, well-tolerated, intestinal form of schistosomiasis is associated with the establishment and maintenace of a variety of immunoregulatory mechanisms (Colley 198 1, Nash et al 1982, Damian 1984. The host anti-egg inflammatory response has been shown to be highly regulated by suppressive mechanisms in long term chronic infections in experimental murine and human schistosomiasis (Colley 1981, Boris 1986, Phillips & Lammie 1986, Doughty et al 1989. It would also appear from studies examining cell-mediated responses, that human patients with hepatosplenic disease (ambulatory, not hospitalized) have unregulated responses to S E A (Colley et al 1986).…”

“…1978, Colley, 1987, Doughty et af. 1987, 1989. These studies suggest that morbidity may be associated with a lack of effective regulation of granulomatous hypersensitivity (Colley et al 1986).…”