Critical role of cytotoxic T lymphocytes in immune clearance of Rickettsial infection

Cytotoxic T-lymphocyte (CTL) activity developed against the major infected target cells of rickettsial infections, endothelial cells and macrophages. Spleen cells from mice immune to Rickettsia conorii exerted specific major histocompatibility complex (MHC) class I-matched CTL activity against R. co norii-infected SVEC-10 endothelial cells, with peak activity on day 10, Sim ilarly, spleen cells from Rickettsia australis-immune mice exerted specific CTL activity against an R. australis-infected macrophage-like cell line. G amma interferon (IFN-gamma) gene knockout mice were more than 100-fold more susceptible to R. australis infection than wild-type C57BL/6 mice. MBC cla ss I gene knockout mice were the most susceptible, more than 50,000-fold mo re susceptible to a lethal outcome of R. australis infection than wild-type C57BL/6 mice, These results indicate that CTL activity was more critical t o recovery from rickettsial infection than were the effects of IFN-gamma. T he observation that perforin gene knockout mice were more than 100-fold mor e susceptible than wild-type C57BL/6 mice indicates that perforin-mediated activity accounts for a large component, but not ail, of the CTL-mediated a ntirickettsial effect. CTL activity was expressed by immune CDS T lymphocyt es. Adoptive transfer of immune CD8 T lymphocytes from IFN-gamma gene knock out mice into R. australis-infected IFN-gamma gene knockout mice dramatical ly reduced the infectious rickettsial content in the organs, confirming tha t CD8 T lymphocytes provide immunity against rickettsiae besides that provi ded by the secretion of IFN-gamma. CTLs appear to be crucial to recovery fr om rickettsial infection.