Turnover of Murine Cytomegalovirus–Expanded CD8⁺ T Cells Is Similar to That of Memory Phenotype T Cells and Independent of the Magnitude of the Response

Abstract

The potential of memory T cells to provide protection against reinfection is beyond question. Yet, it remains debated whether long-term T cell memory is due to long-lived memory cells. There is ample evidence that blood-derived memory phenotype CD8⁺ T cells maintain themselves through cell division, rather than through longevity of individual cells. It has recently been proposed, however, that there may be heterogeneity in the lifespans of memory T cells, depending on factors such as exposure to cognate Ag. CMV infection induces not only conventional, contracting T cell responses, but also inflationary CD8⁺ T cell responses, which are maintained at unusually high numbers, and are even thought to continue to expand over time. It has been proposed that such inflating T cell responses result from the accumulation of relatively long-lived CMV-specific memory CD8⁺ T cells. Using in vivo deuterium labeling and mathematical modeling, we found that the average production rates and expected lifespans of mouse CMV-specific CD8⁺ T cells are very similar to those of bulk memory-phenotype CD8⁺ T cells. Even CMV-specific inflationary CD8⁺ T cell responses that differ 3-fold in size were found to turn over at similar rates.