Direct quantitation of rapid elimination of viral antigen-positive lymphocytes by antiviral CD8(+) T cells in vivo

Lysis of infected cells by CD8(+) T cells is an important mechanism for the control of virus infections, but remains difficult to quantify in vivo. He re, we study the elimination kinetics of viral antigen-positive lymphocytes by antiviral CD8(+) T cells using flow cytometry and mathematical analysis . In mice acutely infected with lymphocytic choriomeningitis virus, more th an 99.99 % of target cells were eliminated each day, corresponding to a hal f-life of 1.4 h. Even in mice exposed to virus 300 days previously, and wit h no ex vivo killing activity, 84 % of the target cells were eliminated per day. Unexpectedly, the elimination kinetics of antigen-positive lymphocyte s was not significantly impaired in mice deficient in either perforin-, CD9 5 ligand- or TNF-mediated cytotoxicity. For viruses with a particular tropi sm for lymphocytes, such as Epstein-Barr virus or HIV, our results illustra te how effectively CD8(+) T cell-mediated elimination of target cells can p otentially contribute to virus control and immunosuppression.