Recruitment and proliferation of CD8+ T cells in respiratory virus infections
Tripp, R.A.; Hou, S.; McMickle, A.; Houston, J.; Doherty, P.C.
Journal of Immunology 154(11): 6013-6021
1995
ISSN/ISBN: 0022-1767 PMID: 7751644 Document Number: 450205
The dramatic increase in the cellularity of the mediastinal lymph nodes (MLN) of mice infected intranasally (i.n.) with influenza viruses is a consequence of both recruitment and proliferation. As many as 20% of 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 HKx3l influenza A virus, the percentage of cycling cells being approximately five times greater for the activated/memory L-selectin-low set than for the naive L-selectin-high population. In addition, substantial evidence of apoptosis was found for CD8+ T cells recovered from the MLN and lung, particularly at 5 and 7 days after infection. Less than 1/1 00 of the proliferating T cells could be shown, by limiting dilution analysis (LDA), to be influenza virus-specific CD8+ cytotoxic T lymphocyte precursors (CTLp). A single, low dose (20 mg/kg) of the DNA-targeted drug cyclophosphamide (Cy) caused a massive decrease in frequency for the responding CD8+ CTLp, though the mice survived infection with the HKx31 virus and there was no long-term exhaustion of the CTLp pool in the MLN, spleen, 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 measure 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.