Recruitment and proliferation of CD8+ T cells in respiratory virus infections.
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 HKx31 influenza A virus, the percentage of of cycling cells being approximately five times greater for the activated/memory 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 1/100 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.
Tripp
R A
RA
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hou
S
S
McMickle
A
A
Houston
J
J
Doherty
P C
PC
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003520:Cyclophosphamide / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010222:Parainfluenza Virus 1, Human; D018184:Paramyxoviridae Infections / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D003520:Cyclophosphamide