Protection to challenge with Trichinella spiralis after primary oral infection in congenitally athymic (nude) mice.

Immunity to Trichinella spiralis infection in laboratory rodents has been regarded as thymus (T)-dependent. Both expulsion of adult T. spiralis worms from the intestinal tract and the number of muscle larvae in the striated musculature have been described as being under the control of T-cell-mediated immunity (Gore et al., 1970, J. Parasitol. 56: 122; Ruitenberg and Steerenberg, 1974, J. Parasitol. 60: 1056-1057; Ruitenberg et al., 1977, Immunology 33: 581587). The same holds true for serum antibody production (Ruitenberg et al., 1977, loc. cit.). Also the inflammatory reaction around the encysted muscle larvae was found to be absent in T-cell-depleted mice (Walls et al., 1973, Clin. Exp. Immunol. 13: 231-242). However, our studies in congenitally athymic (nude) mice of B 1 OLP origin showed both a minor cellular reaction, including IgA containing plasma cells and eosinophils in the small intestine, and a minor local increase of mononuclear cells, mast cells and eosinophils in the striated musculature around encysted larvae (Gustowska et al., 1980, Parasite Immunol. 2: 133-154). Because these athymic (nude) mice lack functional T-cells we postulated that the described reactions, being minor as compared to those observed in euthymic mice, were T-independent. Because we had no evidence for any functional significance of these observations we studied the possible protective effect of a primary oral T. spiralis infection upon a subsequent challenge in this strain of athymic mice. For the experiment we used male SPF B 1 OLP nu/nu mice, approximately 9 wk of age at day 0 of the experiment, obtained from the Central Institute for the Breeding of Laboratory Animals T.N.O., Zeist, The Netherlands, where these mice are produced by continual back crossing with strain B10 OLP. During the experiment the animals were housed in a laminar flow cabinet. The T. spiralis strain used was isolated in 1960 from a pig in Poland and since maintained in our Institute in Wistar rats and from 1972 onwards in Swiss mice. Larvae used for oral infection were obtained from mice infected for 7 wk by artificial digestion for 2 hr (K6hler and Ruitenberg, 1974, Bull. WHO Org. 50: 413-419). To prevent crowding of adult worms, the intestinal phase of the T. spiralis infection was abbreviated with an aqueous solution of 90% v/v of 2-(beta-methoxyethyl) pyridine (Promintic?, Laboratoire Roger Bellon, Neuilly-Seine, France) which was subcutaneously administered at one dose of 5 mg per mouse. The effective dose for killing adult T. spiralis worms is known to be 6 mg, but at this dose our nude mice died within 3 hr after administration. Administering 5 mg per mouse resulted in survival of all treated mice, except one; however, not all adult worms were killed. The time interval of 28 days was chosen on the basis of the kinetics of the IgA cellular reaction in the gut of the athymic mice, found previously (Gustowska et al., 1980, loc. cit.). At the end of the experiment the numbers of adult worms and of muscle larvae were determined. The small intestine was slit lengthwise, rinsed in tap water, and cut into pieces of about 1 cm, which were placed in a Baermann funnel with physiological saline at 37 C for 4 hr. Counting was performed at a magnification of X25. The carcass was cut into small pieces and digested in tap water with 1% HC1 and 1% pepsin (E. Merck, Darmstadt, W. Germany) at 37 C overnight. Counting was performed by dilution and at a magnification of X25. Student's t-test was used to calculate twosided significances of differences between the groups. The experimental design was as follows: the primary infection was given at day 0, abbreviated at day 28 by drug treatment, and parasitological examinations were performed at day 35. The challenge was given at day 35, and parasitological examinations were performed at day 70 (Table I). The results, summarized in Table II, are as follows. Promintic treatment abbreviated ade-