CYTOTOXIC T-LYMPHOCYTES AFTER ORAL IMMUNIZATION WITH ATTENUATED VACCINE STRAINS OF SALMONELLA-TYPHI IN HUMANS

Not only viruses, but certain parasites and bacteria as well, can elic it CTL involved in mediating protection. It has been surmised that CTL able to lyse Salmonella typhi-infected cells are likely to be importa nt in protecting against S. typhi, an intracellular bacterial infectio n, but heretofore this has not been demonstrated. Consequently, the pr esence of CTL activity against S. typhi-infected cells was investigate d in human volunteers immunized with attenuated vaccine strains of S. typhi. Oral immunization with S. typhi strain CVD 908 elicited circula ting CTL effector cells capable of killing S. typhi-infected autologou s EBV-transformed cells. CTL activity was observed after 6 to 8 days o f in vitro expansion in the presence of S. typhi-infected autologous E BV-transformed cells. Maximum CTL activity was observed 29 days after immunization. Depletion of CD8(+) T cells eliminated or markedly reduc ed the CTL activity, while depletion of CD4(+) T cells did not affect CTL responses. CTL activity was blocked by mAbs to human class I MHC A gs, but not by mAbs to class II MHC Ags. This first demonstration that oral immunization of volunteers with attenuated S. typhi elicits CD8( +) T cell, MHC class I-restricted, CTL responses raises the possibilit y that CTL activity might play a significant role in protection during typhoid fever. It also encourages the future use of such attenuated s trains as live vector vaccines to stimulate specific CTL against relev ant foreign Ags.