IMMUNITY AFTER TREATMENT OF HUMAN SCHISTOSOMIASIS - ASSOCIATION BETWEEN CELLULAR-RESPONSES AND RESISTANCE TO REINFECTION

Previous studies have demonstrated the development of an age-dependent resistance to reinfection after chemotherapeutic cure of the helminth ic parasite Schistosoma mansoni. Here we report on a longitudinal inve stigation of cell-mediated responses in infected individuals before an d after treatment which was designed to outline those parameters impor tant in mediating a protective response. A well-defined study group of 89 individuals with an age range of 9 to 35 years was selected from a n area of high S. mansoni transmission in the Machakos district of Ken ya. Peripheral blood mononuclear cell proliferation and cytokine produ ction (interleukin-2 [IL-2], gamma interferon IL-5, IL-4, and tumor ne crosis factor) in response to different crude life cycle-stage antigen s of S. mansoni were assessed longitudinally in vitro before, 3 months after, and 1 year after treatment. Detailed statistical analyses of t he results from this study have indicated a clear negative association between the proliferative responses to adult- and schistosomulum-stag e antigens and subsequent reinfection intensity in older individuals ( 14 to 35 years) which was not present in the younger individuals (9 to 13 years). This association was significant even after the effects of age, sex, and exposure had been accounted for in multiple regression analyses. Cytokines were detected predominantly in response to adult w orm and egg antigen extracts. An inverse association between the two c ytokines gamma interferon and IL-5 was detected in response to all ant igens at the three time points investigated, indicating cross-regulati on in the production of these two mediators. Differences in antigen-sp ecific cytokine levels between the two age groups were detected, with significantly higher IL-5 levels detected in the older (more resistant ) age group. An inverse correlation between this cytokine and reinfect ion was detected but could not be dissociated from the effects of age and exposure in multiple regression analysis.