Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non-parasite antigen.

Schistosoma mansoni infection in the mouse has been shown to be accompanied by a down-regulation in parasite-Ag- and mitogen-induced Th1 cytokine secretion (IL-2 and IFN-gamma) with a simultaneous increase in the production of Th2 cytokines (IL-4, IL-5, and IL-10), suggesting a generalized imbalance in lymphocyte function. In the present study, we examined whether infection with S. mansoni would also influence the character of immune responses to a non-parasite Ag, sperm whale myoglobin (SwMb). When spleen cells (SC) from schistosome-infected SwMb-immunized animals were stimulated with SwMb, their production of IL-2 and IFN-gamma per CD4+ cell was found to be significantly reduced (by 45% and 59%, respectively) compared with the responses observed in immunized uninfected animals. Moreover, SwMb-induced secretion of IL-4 per CD4+ cell was increased threefold in SC cultures from infected mice. No myoglobin-induced IL-5 was detected in the same cultures. Addition to SC cultures of a neutralizing mAb specific for IL-10 partly restored the suppressed IFN-gamma response to SwMb seen in infected mice, suggesting a role for IL-10 in the observed down-regulation. S. mansoni-infected mice also showed an impaired antibody response to SwMb, with levels ranging from 10% to 27% of those observed in uninfected mice, although no differences in IgG isotype were evident. Taken together, these results suggest that infection with S. mansoni induces a down-regulation of Th1 responses and elevation of Th2 responses to unrelated foreign immunogens as well as to parasite Ag themselves. One implication of these findings is that helminth-infected individuals may have altered cell-mediated immune function to other microbial agents.

Immune responses during human schistosomiasis mansoni. III. Regulatory effect of patient sera on human lymphocyte blastogenic responses to schistosome antigen preparations

The in vitro lymphocyte blastogenesis capabilities of patients with schistosomiasis mansoni were tested against phytohemagglutinin (PHA), Candida albicans extract,and soluble preparations of schistosome eggs (SEA), adult worms (SWAP), or cercariae (CAP). When patients lymphocytes were cultured un medium which contained 5 percent human (homologous) normal (uninfected) serum, they responded well to PHA and Candida extract. The responses induced by SEA were maximal in patients with early Schistosma mansoni infections, while reactivity against SWAP and CAP increased during chronic infection. These responses, induced by the Schistosome-derived antigenic preparations,were suppressed if the homologous normal serum supplement of the culture medium was replaced with either the patient's own (autologous) serum, or that of another S. mansoni patient. All sera were heat-inactivated (56 degree C/ 30 min) prior to use. In contrast, responses against the non-specific mitogen (PHA) and the unrelated antigen (Candida extract), were not altered by these changes of the serum supplementation of the media. The degree of suppression by patient serum was not changedby increasing the serum percentage in the medium from 5 percent to 25 percent. The suppressive effects of patient sera on responses induced by SEA and SWAP were increased in relationship to the duration of the serum donor's S. mansoni infection. Preincubation of lymphocytes in suppressive patient sera for 30 min at 37 degree C did not reduce the expected level of responsiveness if the cells were subsequently cultured in homologous-normal serum supplemented medium. The data indicate that during S. mansoni infection patients develop serum component(s) which specifically interfere with the responsiveness of their lymphocytes in regard to certain schistosome-derived antigenic preparations. The immunoregulatory events described could participate in the modulation of immunopathology, the maintenance of chronic worm survival and the prevention of full expression of protective immune responses. (AU)