Effect of Immune Reconstitution on Resistance to Brugia pahangi in Congenitally Athymic Nude Mice

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Abstract
The dichotomy of resistance to B. pahangi between nonsusceptible euthymic C3H/HeN mice, heterozygotic for the nu gene (+/nu), and susceptible, congenitally-athymic nude (nu/nu) C3H/HeN mice, suggests that resistance is thymus-dependent. To test this hypothesis, the effect of syngeneic neonatal thymus grafts and neonatal thymus cell suspensions on recovery of worms at day 40 PI [post infection] and responses to concanavalin A (Con A) were examined in reconstituted nudes. Nude recipients of a thymus graft 7 or 14 wk before s.c. inoculation with 50 infective larvae (L3) yielded no worms and responded strongly to Con A. Serum from these mice reacted in 2 lines of identity with serum from similarly-infected heterozygotes by double radial immunodiffusion against an adult worm saline extract. Nude recipients of a thymus 2 days or 3 wk before inoculation harbored an average of 3 or 2 worms, respectively. I.v. injection of nude recipients with 107 or 108 neonatal thymus cells seven weeks before inoculation was less effective in conferring resistance to B. pahangi and responsiveness to Con A. Complete resistance to B. pahangi could be adoptively transferred to nude mice by 108 spleen cells obtained from infection-primed heterozygotes and injected i.v. on the day of larval inoculation. The same numbers of unprimed spleen cells were less effective when injected 3 wk before inoculation, although numbers of worms were significantly reduced. Passive transfer of primed heterozygote serum, containing high titers of antibodies to adult worm and larval antigens, failed to protect nude recipients against a larval inoculum in the absence of cellular reconstitution. Apparently resistance to B. pahangi in mice is the consequence of complex thymus-dependent immune responses, and that the nude mouse-B. pahangi system will be a useful new model for the study of mechanisms of protective immunity to lymphatic filarial parasites.