We have reported elsewhere (1) 1 that normal human eosinophils adhere to schistosomula of Schistosoma mansoni, in the presence of heat-inactivated sera from patients with schistosomiasis, to a much greater extent than do neutrophils. This finding was surprising, because neutrophils are generally considered to bear more Fc receptors (FcR) for bound IgG than do eosinophils (2-5). On further study, it became apparent that the initiation of adherence by both cell types was a temperature-independent reaction involving the cells' FcR, and that the eosinophil, but not the neutrophil, then underwent a further, temperature-dependent step which rendered its binding progressive and irreversible, 1We considered that this preferential binding of eosinophils to antibody-coated schistosomula might, in part, account for the selective damaging effect of the eosinophil, in comparison with the neutrophil (1), and that it was therefore important to study the mechanism of the irreversible step in more detail. Earlier work by ourselves (6-8) and others (9, 10) had shown that damage induced by eosinophils was associated with cell attachment, followed by degranulation and the release of granule contents onto the surface of the organism. This damage was attributable, at least in part, to the release of one major component of the eosinophil granule, the major basic protein (MBP) 2 (1 1, 12), onto the surface of the organism (13). In contrast, adherent neutrophils showed no signs of degranulation detectable at the electron microscopical level: instead, these cells formed fusions with the outer bilayer of the schistosomulum 2 Abbreviations used in this paper: Con A, eoncanavalin A; E/LAC, Earle's balanced salt solution with 0.5% lactalbumin hydrolysate; FCS, fetal calf Serum; HBSS, Hanks' balanced salt solution; MBP, eosinophil major basic protein; MEM, Eagle's minimal essential medium; NEM, n-ethylmaleimide; PBS, phosphatebuffered saline, pH 7.4. 1456J. Exp. MED.

A method was developed for coupling a hapten, trinitrophenyl (TNP), to the surface of schistosomula of Schistosoma mansoni which results in a minimal loss in their viability as judged by morphological examination in vitro and survival after injection in vivo. Skin-stage (3-h-old) and lung-stage (5-d-old) schistosomula surface labeled in this manner were then compared for their susceptibility to killing by anti-TNP antibody-dependent effector mechanisms both in vivo and in vitro. TNP skin-stage larvae were readily rejected in mice actively immunized against TNP bovine gamma globulin and were highly susceptible to anti-TNP-dependent killing mediated either by complement or purified human eosinophils in vitro. In contrast, TNP-lung-stage schistosomula, which were shown by microfluorimetry to bind anti-TNP antibody to approximately the same extent as skin-stage schistosomula, were found to be resistant to killing by the same in vivo and in vitro mechanisms. These findings suggest that the insusceptibility of postskin-stage schistosomula to antibody-dependent killing must result at least in part from an intrinsic structural change in the integument of the parasite and cannot be caused solely by the masking of parasite antigens by acquired host molecules, a mechanism of immune evasion previously proposed for schistosomes.

The relative importance of cell-mediated inflammatory responses and antibody-mediated responses in controlling parasitic helminth infection is debated. To study the relationship between these responses and resistance or susceptibility to primary Trichinella spiralis infection, we infected resistant AKR mice and susceptible B10.BR mice and analyzed the lymphokines IL-2, IFN-gamma, and IL-5 produced by their T cells as a function of time and lymphoid organ. IL-2-secretors occurred maximally between days 3 and 6 postinfection, whereas IL-5-secretors peaked between days 6 and 9. Previously, we found that IFN-gamma producers peaked before day 6, whereas IL-4 producers peaked between days 6 and 9. Most cytokine secretors were CD4+. The simultaneous development of IL-2- and IFN-gamma-secreting cells, and IL-4- and IL-5-secreting cells, suggests that the infection may be stimulating T cells to differentiate into cells capable of secreting specific cytokine sets, analogous to the postulated Th1 and Th2 subsets. In the spleen and mesenteric lymph nodes, cells from B10.BR mice secreted more IL-5 than cells from AKR mice, as we found previously for IL-4. For both strains, mesenteric lymph node cells produced more IL-5 than splenocytes. The AKR mesenteric lymph node cells produced more IL-2 than the B10.BR cells, but the reverse occurred in splenocytes. The AKR peripheral lymph node cells also secreted more IFN-gamma than the B10.BR cells, but the strains were equivalent for peritoneal exudate cell IFN-gamma production. Thus, the lymphoid organ microenvironment plays an important role in regulating cytokine-secreting cell development in this system. We also tested the possible regulatory role of IL-1. Exogenous rIL-1 alpha increased IFN-gamma secretion early but not late in mesenteric lymph node cells from both strains; this reflected an increased IFN-gamma-secreting cell frequency, not a change in IFN-gamma mRNA transcript level. Exogenous rIL-1 alpha did not consistently affect IL-2, IL-4, or IL-5 secretion. These data suggest that IL-1 alpha availability in vivo may regulate IFN-gamma-secreting cell development. In sum, early activation of IFN-gamma-secreting T cells in lymph nodes, with little subsequent activation of IL-4- and IL-5-secreting cells, distinguished the resistant from susceptible strain responses to T. spiralis infection, and IL-1 alpha and lymphoid organ environment influence IFN-gamma-secreting cell activation.