The role of antigen-independent persistence of memory cytotoxic T lymphocytes

We use mathematical models to analyze the role of a memory cytotoxic T lymp hocyte (CTL) response in viral infections. The model predicts that antigen- independent persistence of an elevated number of precursor CTL (CTLp) does not protect the host from clinical symptoms upon re-infection. Instead, we find that antigen-independent long-term persistence of CTLp is required to clear virus infections. This mechanism also applies to infection in hosts t hat have never experienced the pathogen before. Requirement of antigen for the long-term maintenance of CTLp results in failure to clear the infection , even in hosts characterized by a high CTL responsiveness. We compare the CTL model to a B cell model. In keeping with experimentally established fin dings, B cells are efficient in protecting against re-infection, but are un likely to clear viral infections unless the virus is cytopathic. We conclud e that the role of 'memory CTLp' is different from the role of memory B cel ls in viral infections: antigen-independent long-term persistence of CTLp i s a pre-requisite to ensure clearance of infection.