Persistent MCMV infection drives continuous production of short‐lived effector CD8 T cells

Abstract

Murine cytomegalovirus is a beta herpesvirus that establishes chronic infection in mice driving a huge CD8+ T cell response that is maintained for the life of the host with little or no evidence of T cell exhaustion. The MCMV‐specific CD8 T cell population can be divided into 2 categories based on antigen specificity: “inflating” and “non‐inflating”. We wished to understand how these two populations were driven and addressed this with a series of adoptive transfer experiments. Non‐inflating T cells crash after acute infection and persist by slow division during chronic infection with a central memory‐like phenotype, behaving as if the virus were cleared. In contrast, inflators resemble effector memory T cells and increase dramatically in number shortly after acute infection. Our data suggest that inflation results from a combination of cell division and recruitment of naive T cells. At late times however, the rate of inflation slows and the large effector memory population is maintained. Strikingly, most inflated cells at these time points no longer divide and have a short life‐span (t1/2 ~45–60 days) that is independent of viral antigen, similar to what has been described as short‐lived effectors. Our data suggest that the overall population is maintained by recruitment of naïve cells that join this short‐lived pool. Yet there is real memory within this population since new infection drives extensive, rapid division.