The regulation of lymphoid function during schistosomiasis: influence of T-cell-derived suppressor molecules on antigen recognition, cellular activation and granuloma formation.

Abstract

We have previously studied a T-cell derived soluble suppressor factor (TseF) which regulates immunopathology in schistosomiasis. The current studies address the mechanism whereby TseF suppresses the functional immune response in murine schistosomiasis. We assessed three stages of the immune response: (1) initial antigenic recognition using the criteria of antigen-mediated cell division or blast transformation (AMBT); (2) intracellular differentiation utilizing criteria of glutathione (GSH) and ornithine decarboxylase (ODC) production; and (3) efferent function utilizing criteria of in vitro granuloma formation (IVGF). We studied these three criteria of immune reactivity during the course of schistosomiasis. Lymphoid cells from acutely infected animals demonstrated high levels of antigen-mediated cell division and in vitro granuloma formation; ODC and GSH levels were low. Cells obtained from chronically infected animals demonstrated lower antigen-mediated cell division and granuloma formation; however, ODC and GHS levels were much higher, indicating that cells obtained from chronically infected animals are in a non-reactive state of increased activation. TseF strongly increased GSH and ODC levels in lymphocytes obtained from acutely infected animals, and this effect was augmented by the presence of antigen. However, TseF had minimal effects on initial antigenic recognition, and profoundly suppressed the effector function. The relationship between the effects of TseF on antigen recognition and function was regulated at the clonal level. TseF function required the generation of GSH. Since TseF is produced in chronic disease under conditions of decreased immunological reactivity, the alterations of GSH and ODC activity, induced by TseF, may be responsible for the regulation of immunopathology.