Mechanism of induction of cell-mediated immunity to virus infections: in vitro inhibition of intracellular multiplication of mouse adenovirus by immune spleen cells.

Mice were protected from lethal infection with mouse adenovirus (M-Ad) by adoptive transfer of immune spleen cells (ISC) that were prepared from mice immunized with M-Ad and not protected by sonicated ISC. However, a similar extent of protection was also observed by passive immunization with anti-M-Ad serum. In contrast, by in vitro experiments ISC were shown to be able to interrupt intracellular multiplication of M-Ad, whereas sonicated ISC, unimmunized mouse spleen cells, or anti-M-Ad serum were unable to do so. ISC were inhibitory in vitro when added within 12 h postinfection but not when added later. The inhibitory activity of ISC was regarded as due to cell killing by ISC, since the trypan blue exclusion test showed that above 80% of infected cells were killed by ISC even when 5'-fluorodeoxyuridine was added to the cells to block viral deoxyribonucleic acid synthesis, under which conditions control infected cells, to which ISC were not added or normal spleen cells were added, were kept alive at least for a few days. Kinetics studies in M-Ad-infected mice showed that the inhibitory activity of ISC became highest at 1 to 2 weeks postinfection and faded away thereafter in a few weeks, whereas serum antibody titer assayed by passive hemagglutination reached its peak level at about 4 weeks postinfection and declined gradually therafter.