Cutting edge: Virus-specific CD8+ T cell clones and the maintenance of replicative function during a persistent viral infection.
Persistent viral infections induce the differentiation and accumulation of large numbers of senescent CD8(+) T cells, raising the possibility that repetitive stimulation drives clones of T cells to senesce. It is therefore unclear whether T cell responses are maintained by the self-renewal of Ag-experienced peripheral T cell subsets or by the continuous recruitment of newly generated naive T cells during chronic infections. Using a transgenic mouse model that permits the indelible marking of granzyme B-expressing cells, we found that T cells primed during the initial stages of a persistent murine γ-herpes infection persisted and continued to divide during a latent phase of up to 7 mo. Such cells maintained an ability to extensively replicate in response to challenge with influenza virus expressing the same Ag. Therefore, Ag-experienced, virus-specific CD8(+) T cell populations contain a subset that maintains replicative potential, despite long-term, persistent antigenic stimulation.
Wellcome Trust Immunology Unit, University of Cambridge, Cambridge, United Kingdom.
Oliver
O
Bannard
Matthew
M
Kraman
Douglas T
DT
Fearon
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D053804:Granzymes / Q000096:biosynthesis / Q000276:immunology*; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018144:Rhadinovirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000956:Antigens, Viral; D053804:Granzymes; C509214:Gzmb protein, mouse