CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria

Immunization of BALB/c mice with radiation-attenuated Plasmodium yoelli sporozoites induces cytotoxic T lymphocytes (CTL) specific for an epitope located within the amlno acid sequence 277-288 of the P. yoellicircumsporozoite (CS) protein. Several CD8 + CTL clones were derived from the spleen cells of sporozolte-immunlzed mice, all displaying an apparently identical epitope specificity. All the clones Induced high levels of cytotysls in vitro upon exposure to peptide-incubated MHC-compatlble target cells. The adoptive transfer of two of these clones conferred complete protection against sporozotte challenge to naive mice. This protection Is species and stage specific. Using P. yoelli specific ribosomal RNA probes to monitor the in vivo effects of the CTL clones, we found that their target was the intrahepatocytic stage of the parasite. The protective clones completely Inhibited the development of the liver stages of P. yoelli Some CTL clones were only partially Inhibitory in vivo, while others failed completely to alter liver stage development and to confer any detectable degree of protection. The elucidation of the effector mechanism of this CTL mediated protection against rodent malaria should facilitate the design of an effective malaria vaccine. From a broader perspective this model may provide further insight into the mechanlsm(s) of CTL mediated killing of intracellular non-viral pathogens in genera