NONSPECIFIC IMMUNE-RESPONSES AND MECHANISMS OF RESISTANCE TO EIMERIA-PAPILLATA INFECTIONS IN MICE

Severe combined immunodeficient (SCID)-beige mice inoculated,vith the intracellular parasite Eimeria papillata produced significantly more o ocysts during primary infections than inoculated immunodeficient SCID mice. Therefore, the addition of the beige mutation, which detrimental ly affects neutrophil and natural killer (NK) cell functions, enhanced the parasites' ability to reproduce within the small intestine, To id entify which of these two cell types is responsible for a protective i mmune response during primary infection, the following groups of mice were inoculated: (i) SCID mice depleted of neutrophils with antigranul ocyte monoclonal antibody (RB6-8C5), (ii) C57BL/6 mice depleted of NK cells with the anti-NK-1.1 monoclonal antibody (PK136), and (iii) tran sgenic Tg epsilon 26(++) mice (T and NK cell deficient), To identify t he mechanisms of immunity during primary and secondary infections, gam ma interferon (IFN-gamma) knockout and perforin knockout mice were ino culated, Oocyst output was found to be significantly higher during pri mary infection for mice depleted of NK cells by administration of anti -NK-1.1 antibodies, for Tg epsilon 26(++) mice, and for IFN-gamma knoc kout mice, During secondary infections, only perforin knockout mice pr oduced significantly more oocysts compared to control mice, Our observ ations suggest that NK cells inhibit E. papillata oocyst output during primary infection by the production of IFN-gamma and that this inhibi tion is independent of perforin. Immunity to reinfection does not requ ire IFN-gamma but appears to be mediated, at least in part, by a perfo rin-dependent mechanism.