CLASS-I RESTRICTED CYTOTOXIC T-LYMPHOCYTES ARE DIRECTLY CYTOPATHIC FOR THEIR TARGET-CELLS IN-VIVO

Although CD8-positive, class I-restricted CTL play a critical role in viral clearance and immunopathology in many model systems, they have n ot been shown to directly kill their target cells in vivo at the singl e cell level. Using a hepatitis B surface Ag transgenic mouse model of class I-restricted, CTL-mediated liver disease, we now demonstrate th at CD8-positive, L(d)-restricted hepatitis B surface Ag-specific CTL b ind and kill their target cells in vivo by triggering them to undergo degenerative cytologic changes compatible with apoptosis. Unexpectedly , the data also indicate that the pathologic consequences of this dire ct, Ag-specific CTL effect are much less severe than the cyclodestruct ive, Ag-nonspecific inflammatory response that they induce when they a re activated by Ag recognition.