Enhanced natural killer cell activity in experimental murine encephalitozoonosis.

Abstract

Spleen cells from mice infected with the protozoan parasite Encephalitozoon cuniculi demonstrated enhanced in vitro cytolysis of YAC-1 lymphoma cells. Selective cell depletion experiments showed that the dominant cell population mediating cytolysis of YAC-1 tumor cells expressed the characteristic phenotype of murine natural killer (NK) cells because (i) pretreatment of spleen cells with anti-asialo GM 1 antiserum plus complement abolished the cytotoxic activity; (ii) augmented cytolysis was found in athymic nude mice; (iii) pretreatment of spleen cells with anti-Thy 1.2 plus complement did not affect the level of cytolysis; and (iv) nylon wool removal of adherent cells did not reduce the augmented cytolysis. The augmented cytolysis peaked 7 days after infection, gradually diminished, and finally returned to control levels by 21 days postinfection. The parasite-induced augmentation of NK cell activity was dose-dependent: inoculation of 10(7) parasites gave maximum enhancement, whereas 10(5) or 10(4) parasites had an insignificant effect on spontaneous NK cell cytolysis. The augmented NK cell cytotoxicity was dependent upon viable parasites; inoculation of killed parasites failed to stimulate a significant increase in spontaneous cytolysis. An active infectious process was an important component of this process. The peak of NK activity in euthymic mice was closely correlated with the active stage of infection, and reduction of NK cell activity coincided with recovery from infection. By contrast, athymic nude mice were unable to control E. cuniculi infections yet maintained persistently elevated NK responses. The present data, along with previous reports, indicate that infection with E. cuniculi evokes transient modulation of host immune functions.