INDUCTION OF CD8-CELLS BY IMMUNIZATION WITH KILLED INFLUENZA-VIRUS AND EFFECT OF CHOLERA-TOXIN B-SUBUNIT( CYTOTOXIC T)

The MHC class I cytotoxic T-lymphocyte (CTL) response in mice given fo rmalin-inactivated influenza whole-virus vaccine (WVV) with or without cholera toxin B subunit (CTB) was studied. Intraperitoneal injection of Balb/c (H-2d) mice with high doses of A/Taiwan/1/86 (H1N1) WVV stim ulated influenza A virus-specific CTL response in a dose-dependent man ner. A dose of 4.4 or 44 mug induced CTL response equal to or greater than live influenza virus infection. Coadministration of vaccine with 5 or 25 mug of CTB resulted in a higher level of CTL than with vaccine alone. CTL lysed A/Taiwan and A/Shanghai (H2N2) virus-infected class I-expressing P815 (H-2d) but not virus-infected EL-4 (H-2b) target cel ls nor B/Yamagata virus-infected target cells. virus-infected MHC clas s II- and class I-expressing A20 (H-2d) targets were also lysed. Deple tion of Lyt-2+ (CD8+) T cells with monoclonal antibody completely abro gated lysis of P815 target cells and resulted only in a slight reducti on of lysis of A20 target cells. Depletion of L3T4+ (CD4+) T cells or NK cells had minimal effect on lysis of either P815 or A20 target cell s. Using limiting dilution analysis, the precursor CTL (pCTL) frequenc y paralleled CTL activity. Significant CTL activity was detected 7 mon ths after immunization. These results demonstrate that adequate doses of influenza WVV with or without CTB can induce long-lasting influenza A cross-reactive MHC class I-restricted CD8+ CTL response in mice. Th us, coadministration of influenza WVV with CTB may lead to an effectiv e vaccine that stimulates both CTL and antibody responses.