The sensitization of mice with a wild-type and cold-adapted variant of influenza A virus. II. Secondary cytotoxic T cell responses

Reductions in virus titers and the generation of enhanced cytotoxic T cell (Tc) activity in the lungs of mice primed either with a wild-type, parental (H2N2) influenza virus, A/AA/6/60, or a cold-adapted variant A/AA/6/60-ca and challenged 6 weeks later with a H1N1 A/WSN virus showed that both H2N2 viruses could sensitize the mice. A comparison of graded sensitizing doses of each virus showed that inocula of 10⁶ tissue culture infective doses (TCID₅₀) of the ca-variant or 10³ TCID₅₀ of the wild-type virus gave similar results. The spleens and lungs of normal mice were found to contain similar levels (circa 1/10⁵ cells) of precursor Tc cells and the level in the lung did not increase 2 days after intranasal (i.n.) inoculation of A/WSN virus. Two and 6 weeks after priming mice with 10⁵ TCID₅₀ of either virus, the lungs contained a 20-fold increase in the precursor Tc cell frequency. In contrast, sensitization with a sub-lethal dose of mouse-adapted A/WSN virus caused a 100-fold or greater increase. Sensitization of mice with the parental but not the ca-variant virus caused an increase in frequency of precursor Tc cells in the spleens of the sensitized mice and this might reflect the very low level of replication of the ca-variant virus in the mouse lung.