Virus-specific CD8+ T-cell memory determined by clonal burst size

Nature
S HouP C Doherty

Abstract

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 v...Continue Reading

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