RECRUITMENT AND PROLIFERATION OF CD8(-CELLS IN RESPIRATORY VIRUS-INFECTIONS() T)

The dramatic increase in the cellularity of the mediastinal lymph node s (MLN) of mice infected intranasally (i.n.) with influenza viruses is a consequence of both recruitment and proliferation. As many as 20% o f the CD8(+) subset in the MLN can be shown to be in S or G2 + M phase at 6 days after i.n. challenge with the HKx31 influenza A virus, the percentage of of cycling cells being approximately five times greater for the activated/memory L-selectin-low set than for the naive L-selec tin-high population. In addition, substantial evidence of apoptosis wa s found for CD8(+) T cells recovered from the MLN and lung, particular ly at 5 and 7 days after infection. Less than 1/100 of the proliferati ng T cells could be shown, by limiting dilution analysis (LDA), to be influenza virus-specific CD8(+) cytotoxic T lymphocyte precursors (CTL p). A single, low dose (20 mg/kg) of the DNA-targeted drug cyclophosph amide (Cy) caused a massive decrease in frequency for the responding C D8(+) CTLp, though the mice survived infection with the HKx31 virus an d there was no long-term exhaustion of the CTLp pool in the MLN, splee n, or lung. The Cy treatment was also followed by a smaller reduction in the prevalence of memory CTLp (specific for Sendai virus) that were present concurrently in the regional lymph node, indicating that a me asure of bystander activation is occurring. The experiments show that respiratory virus infections have no negative impact on established T cell memory, and that there is no phase of transient exhaustion in the acute virus-specific CTLp response in this localized infection.