Our paper is highly cited because it speaks to two important issues: 1) Memory CD8 T cell lineage development is intensely studied and our data shows that lineage choice can be altered by controlling factors early in the immune response to infection and 2) Adoptive transfer of TCR transgenic T cells is a widely used technique and we show that care must be taken in using this system, especially when studying memory T-cell development. This is a result of our finding that naive T cell frequency can greatly affect the developmental pathway of memory T cells.

This paper provides a definitive model on which to base memory CD8 T cell development. The findings revolve around the definition of the developmental link between central versus effector memory T-cell subsets and further defines a critical step in functional differentiation of effector memory cells.

The development of immunological memory by vaccination or prior infection provides one with long-lasting protection from dangerous pathogens. Our results demonstrate a way in which memory development could be manipulated to provide "designer" memory cells with preference for migrating to one location or another. In this way, with appropriate vaccination strategies, our defensive capabilities could be tailored to respond more effectively to different types of infection.

We have a long standing interest in the factors that regulate both the induction and maintenance of memory CD8 T-cells. This particular work originally stemmed from our previous studies showing that different memory CD8 T-cell subsets were localized to lymphoid versus non-lymphoid tissues. That work led to testing the hypothesis that the memory subsets represent distinct, rather than interconvertible lineages.

The problems encountered were primarily due to the large number of animals and cell sorting that was required to address the problem. Many long hours were spent in front of the flow cytometer for sorting as well as analysis of small numbers of recovered cells.