title: Developing and maintaining protective CD8+ memory T cells.
abstract: A critical aim of vaccine-related research is to identify the mechanisms by which memory T cells are formed and maintained over long periods of time. In recent years, we have designed experiments aimed at addressing two key questions: (i) what are the factors that maintain functionally responsive CD8+ memory cells over long periods of time, and (ii) what are the signals during the early stages of infection that drive the differentiation of long-lived CD8+ memory T cells? We have identified a role for CD4+ T cells in the generation of CD8+ T-cell-mediated protection from secondary challenge. While CD4+ T cells appear to play a role in the programme of CD8 memory, we find that they are also required for the long-term maintenance of CD8+ memory T-cell numbers and function. This property is independent of CD40-CD40L interactions, and we propose a role for CD4+ T cells in maintaining the ability of CD8+ memory T cells to respond to interleukin-7 (IL-7) and IL-15. By manipulating both the time course of infection and the timing of antigen presentation to newly recruited CD8+ T cells, we also demonstrate that the programming of effector and memory potential are at least partially distinct processes.
authors.affiliation: Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Williams
authors.forename: Brittany J
authors.initials: BJ
authors.lastname: Holmes
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Sun
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bevan
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007239:Infections / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic