GOBLET CELL MUCINS AS THE SELECTIVE BARRIER FOR THE INTESTINAL HELMINTHS - T-CELL-INDEPENDENT ALTERATION OF GOBLET CELL MUCINS BY IMMUNOLOGICALLY DAMAGED NIPPOSTRONGYLUS-BRASILIENSIS WORMS AND ITS SIGNIFICANCEON THE CHALLENGE INFECTION WITH HOMOLOGOUS AND HETEROLOGOUS PARASITES

The aim of this study was to examine the role of T cells on the altera tion of terminal sugars of goblet cell mucins in the small intestinal mucosa of parasitized rats and to clarify the biological significance of the altered mucins in the mucosal defence against intestinal helmin ths. For this purpose, Nippostrongylus brasiliensis adult worms obtain ed from donor rats at 7 ('normal' worms) or 13 days ('damaged' worms) post-infection were implanted intraduodenally into euthymic and hypoth ymic (rnu/rnu) rats. Expulsion of implanted normal worms and associate d goblet cell changes were extremely delayed in hypothymic recipients compared with euthymic recipients. In contrast, intraduodenally implan ted damaged worms were expelled by day 5 regardless of the strains. Ar ound the time of expulsion of implanted damaged worms, euthymic recipi ents showed both goblet cell hyperplasia and alteration of mucins, whe reas hypothymic rats showed only the latter. Dexamethasone treatment c ompletely abolished goblet cell changes of both strains of recipients. To clarify the importance of the constitutional changes of goblet cel l mucins in mucosal defence, euthymic rats were primed by implantation of damaged worms to induce goblet cell changes, and then 3 or 5 days later they were challenged by implantation with normal worms. The resu lts show that when goblet cell changes were induced by priming with da maged worms, recipient rats could completely prevent the establishment of norm;ll worms. When hypothymic rats were primed and challenged in the same manner, a similar but slightly less preventive effect was obs erved. Such a protective effect of altered mucins seems to be selectiv e because priming of euthymic rats with damaged N. brasiliensis did no t affect the establishment of Strongyloides venezuelensis. These resul ts suggest that: (1) once N. brasiliensis adult worm are 'damaged' by the host's T-cell-dependent immune mechanisms, they can induce alterat ion of sugar residues of goblet cell mucins via host-mediated, T-cell- independent processes; (2) the expression of such altered mucins is hi ghly effective not only in causing expulsion of established damaged wo rms but also in preventing establishment of normal worms; and (3) the preventive effect of altered mucins is selective against parasite spec ies.