Development of Immunity in Mice Previously Infected at an Early Age with Nematospiroides dubius

Abstract

Mice given their first of 3 stimulating infections of Nematospiroides dubius at 3 weeks of age and subsequently challenged with N. dubius larvae did not develop immunity. In contrast, mice given the same infection regimen beginning at 4 weeks of age did develop immunity. It appears that functional immunological maturity in this host-parasite system develops between 3 and 4 weeks of age. Mice which were reinfected repeatedly with N. dubius from an early age and which maintained adult worms for prolonged time periods did not develop tolerance. This suggests that the failure of young mice to develop immunity following infection at an early age is not due to tolerance but rather due to lack of functional immunological competence in the host during the initial exposure period. In man and higher vertebrates the neonate host is exposed to a wide variety of parasites. According to the dose and route of antigen inoculation, immunological tolerance to a limited number of antigens has been produced in laboratory animals following neonatal exposure (Leskowitz, 1967). However, there appears to be no concrete evidence that tolerance occurs naturally in the field. Although neonates exposed to gastrointestinal nematodes by oral or parental routes may or may not develop immunity (Gibson, 1952; Miller, 1965; Jarrett et al., 1968), this early conditioning has not been shown to play a role in the response to later infections with the same agent. Neonate as well as adult mice infected with Nematospiroides dubius harbor residual adult stages for as long as 8 months following infection. However, it has been shown repeatedly that the strain of mouse used for this study (a strain of Swiss mice developed in the Department of Parasitology and Laboratory Practice, University of North Carolina at Chapel Hill) develops immunity to this trichostrongylid following a minimum of three infections with 50 N. dubius larvae (Van Zandt, 1961). The purpose of the experiment being reported here was to determine whether or not mice would develop immunity to N. dubius if previously exposed to N. dubius as neonates. Received for publication 19 December 1972. * Aided by NIH Grant AI-10490-02. t Department of Epidemiology and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa. t Youngstown State University, Youngstown, Ohio. MATERIALS AND METHODS The strain of nematode, preparation of cultures, method of inoculation, and counting of adult worms have been described by Van Zandt (1961). As outlined in Table I, 80 female S-W mice, 3 weeks old, were divided randomly into 8 groups of 10 mice (Groups A, B, C, and D, 3-week experimentals; Groups A,, Be, Cc, and Dc, 3-week nonstimulated controls). In a similar manner 80 4week-old mice were divided into 8 groups of 10 mice (Groups E, F, G, and H, 4-week experimentals; Groups Ec, Fc, Gc, and He, 4-week nonstimulated controls). All mice in Groups A and E were given 3 stimulating infections of 50 N. dubius larvae at 14-day intervals. Fourteen days after the 3rd stimulating infection, the mice of both groups were treated with pyrantel tartrate (Cypess and Van Zandt, 1973). Four days after the drug treatment, mice in Groups A and E and Groups Ac and Ec were challenged with an infection of 50 N. dubius larvae. After 14 days all the mice in these 4 groups were killed and the adult N. dubius in the small intestine were counted. The mice of the remaining 12 groups were handled as above except each experimental group received varying numbers of stimulating infections prior to drug treatment and the final challenging infection, i.e., experimental Groups B and F received a total of 4 stimulating infections; Groups C and G, a total of 5 stimulating infections; and Groups D and H, a total of 6 stimulating infections (Table I).