Memory CD8 T-cell compartment grows in size with immunological experience

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Abstract

Memory CD8 T cells, generated by natural pathogen exposure or intentional vaccination, protect the host against specific viral infections1. It has long been proposed that the number of memory CD8 T cells in the host is inflexible, and that individual cells are constantly competing for limited space2,3. Consequently, vaccines that introduce over-abundant quantities of memory CD8 T cells specific for an agent of interest could have catastrophic consequences for the host by displacing memory CD8 T cells specific for all previous infections4,5,6. To test this paradigm, we developed a vaccination regimen in mice that introduced as many new long-lived memory CD8 T cells specific for a single vaccine antigen as there were memory CD8 T cells in the host before vaccination. Here we show that, in contrast to expectations, the size of the memory CD8 T-cell compartment doubled to accommodate these new cells, a change due solely to the addition of effector memory CD8 T cells. This increase did not affect the number of CD4 T cells, B cells or naive CD8 T cells, and pre-existing memory CD8 T cells specific for a previously encountered infection were largely preserved. Thus, the number of effector memory CD8 T cells in the mammalian host adapts according to immunological experience. Developing vaccines that abundantly introduce new memory CD8 T cells should not necessarily ablate pre-existing immunity to other infections.

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Figure 1: Heterologous prime–boost vaccination induces a huge addition of memory CD8 T cells and a permanent increase in the proportion of CD8 + lymphocytes.
Figure 2: Total numbers of CD8 T, CD4 T, and B lymphocytes in the spleen of control mice and mice that have been sequentially immunized with VSV-NJ, VVn and VSV-IND.
Figure 3: Increase among CD8 T cells is due solely to an increase in CD62L lo  CD44 hi memory CD8 T cells.
Figure 4: Addition of very large numbers of memory CD8 T cells induces only modest attrition of pre-existing memory CD8 T cells.

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Acknowledgements

We thank S. Jameson, E. J. Wherry and A. Haase for critical discussions and reading of the manuscript, and J. W. Yewdell for recombinant vaccinia virus. This research was supported by start-up funds from the University of Minnesota Medical School (V.V. and D.M.) and NIH grant AI30048 (R. Ahmed).

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Correspondence to David Masopust.

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Vezys, V., Yates, A., Casey, K. et al. Memory CD8 T-cell compartment grows in size with immunological experience. Nature 457, 196–199 (2009) doi:10.1038/nature07486

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