Vezys et al. reply

Replying to: R. M. Welsh and L. K. Selin Nature 459, 10.1038/nature08091 (2009) We reported that it is possible to increase the total number of memory CD8 T cells within an organism, and to establish preternatural numbers of vaccine-specific effector memory CD8 T cells while preserving naive CD8 T cells and most pre-existing memory CD8 T cells specific for a previously encountered infection https://www.nature.com/articles/nature08091 1. These findings raise new questions regarding the regulation and limits of generating CD8 T cell immunity. Our discussion highlighted three points related to the issue of attrition. First, that it is possible to over-estimate perceived attrition by only examining percentages (see Fig. 1 of ref. 1)2. Second, our vaccine regimen resulted predominantly in the generation of effector memory CD8 T cells located outside of lymph nodes. It remains possible that the number of lymph node central memory T cells remains tightly regulated. Third, we noted that our data did not refute that attrition could happen under a variety of circumstances. However, our data demonstrate that attrition is not an axiomatic property of immunization, mandated by stringent regulation of the size of the total memory CD8 T-cell compartment. Indeed, we saw no evidence of attrition after single infections with a virus (vaccinia), an intracellular bacteria (Listeria monocytogenes) and a parasite that induces massive splenomegaly (Plasmodium yoelii), and observed comparatively little attrition after a heterologous prime–boost regimen involving successive immunization with three viruses1.