Virus-specific CD8+ T-cell memory determined by clonal burst size.
Although some viruses, particularly the herpes viruses, may never be eliminated from the body, others like influenza A, regularly reinfect humans and boost waning crossreactive CD8+ T-cell immunity. Prolonged T-cell memory is found for viruses that are unlikely to be re-encountered and which do not persist in the host genome, indicating that CD8+ T-cell memory might be independent of continued (or sporadic) antigenic exposure. A feature of virus-specific CD8+ T-cell memory is that antigen-specific cytotoxic T-lymphocyte precursors (CTLp) are greatly increased and remain high throughout life. The idea that persistence of the inducing antigen is essential is based on experiments in which adoptively transferred CD8+ memory T cells could not be detected for more than a few weeks in naive recipient mice without secondary challenge. Here we show that restimulation of such chimaeric mice with an inducing Sendai virus antigen increases the clonal burst size more than 7-fold within 8 days, making memory CTLp easier to detect in the longer term. We find that Sendai-virus-specific CTLp are maintained for > 250 days in irradiated uninfected recipients, including reconstituted beta 2-microglobulin-/- mice. To determine whether a source of viral peptide can persist after primary infection, we gave Sendai-virus-specific Thy1.1+ memory spleen cells to naive mice that had been minimally depleted of Thy1.2+ T cells, or to comparable recipients that had recovered from infection with Sendai virus or influenza virus. Although antibody against Sendai virus was never found in the naive recipients, Sendai-virus-specific CD8+ memory T cells were maintained equally well in each case for > 100 days after cell transfer. We find no evidence for persisting depots of viral protein that might feed into the endogenous processing pathway and maintain virus-specific CD8+ T-cell memory.
Hou
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Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee 38105.
Hyland
L
L
Ryan
K W
KW
Portner
A
A
Doherty
P C
PC
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D016827:CD8 Antigens; D002470:Cell Survival; D000939:Epitopes; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D010222:Parainfluenza Virus 1, Human / Q000276:immunology*; D016897:Respiratory Burst; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation
D000956:Antigens, Viral; D016827:CD8 Antigens; D000939:Epitopes