Attrition of memory CD8 T cells

Arising from: V. Vezys et al. Nature 457, 196–199 (2009)10.1038/nature07486 ; Vezys et al. reply An important role for the immune system is to maintain protective immunological memory to a wide variety of pathogens encountered over one’s lifetime, while still leaving the host able to respond to newly encountered pathogens. Vezys et al.1 make the interesting observation that it is possible to repeatedly immunize mice in ways that allow for development of high numbers of memory CD8 T cells without depleting pre-existing memory cells specific for other pathogens. This study, which offers promise in developing potent vaccination schemes, is seemingly at odds with work published by us in the 1990s showing a loss in CD8 memory cells after a series of infections2,3. In their reply, Vezys et al. mention that we may have misinterpreted our data because we reported the putative loss of memory T cells as per cent rather than total number, but here we represent the data in those studies as total cell number2,3,4. We show here in Fig. 1 that a series of infections can indeed reduce the total number of memory cells, indicating that vaccination strategies need to consider this issue. Figure 1 Depletion of memory CD8 T cells by heterologous viral infections. Total numbers of lymphocytic choriomeningitis virus (LCMV)-epitope-specific CD8 T cells per spleen in mice immune to LCMV and subsequently infected with Pichinde virus (PV), vaccinia virus (VV), murine cytomegalovirus (MCMV) or vesicular stomatitis virus (VSV). Data are reworked from refs 3 and 4. These are controlled experiments in which all measurements were taken at the same time after LCMV infection. a, Attrition of LCMV-specific memory cells as measured by limiting dilution assays after sequential virus infections. b, Attrition of LCMV-specific memory cells as measured by MHC-dimer or intracellular IFN-γ assays after sequential virus infections. Combined frequencies of T cells specific to LCMV-encoded epitopes NP396, GP33/34 and GP276 (GP, glycoprotein; NP, nucleoprotein). PowerPoint slide