Production of DTH in the Mouse to Influenza Virus: Comparison with Conditions for Stimulation of Cytotoxic T Cells

Abstract

The kinetics of sensitization and elicitation of delayed-type hypersensitivity in mice to both infectious and non-infectious preparations of influenza virus was found to be similar to that of some protein antigens and to other viruses. Sensitization was achieved without added adjuvant. Maximum DTH was elicited in the footpad 6 days after sensitization. Adoptive transfer experiments showed that the effector cells were in the Ig-negative fraction of the spleen and were sensitive to anti-θ and complement. A comparison was made of conditions for the generation of DTH activity with cytotoxic T cells. The route of inoculation was important. With a high dose (10³ HAU) of virus, subcutaneous inoculation was the most efficient and intravenous injection the least efficient for sensitizing for DTH, whereas the reverse was found for cytotoxic T-cell generation. Second, treatment of mice with cyclophosphamide (Cy) had differential effects. Preinjection of a large dose (200 mg/kg) into mice 2 days before sensitization with virus resulted in an increase In the DTK response and a 90% reduction in cytotoxic T-cell activity in the spleens of the treated mice. The Cy-injected mice had reduced (70%) anti-haemagglutinin levels compared with the controls. This may be the explanation for the enhanced DTH response, since transfer of specific antibody to sensitized mice before injection of the eliciting virus substantially reduced the DTH response. Pretreatment with Cy did not affect the generation of DTH effector cells, since spleen cells from these and control mice had similar levels of activity.