title: Kinetic and mechanistic requirements for helping CD8 T cells.
abstract: The requirements for the generation of fully competent long-lived memory CD8 T cells and in particular the role and the mechanisms of help from CD4 T cells remain ill-defined. Memory CD8 T cells generated in the absence of CD4 T cell help often have an impaired recall proliferation and are thus unable to confer protection against certain pathogens. However, the timing and the mechanisms involved in the delivery of help are still unclear and differ between various experimental systems. In this study, we investigated the role of CD4 T help in generating memory CD8 T cells in a defined heterologous prime-boost system, consisting of priming with replication incompetent virus-like particles and challenge with recombinant vaccinia virus, both sharing only a common lymphocytic choriomeningitis virus-derived CD8 T cell epitope. We show in this system that delivery of help is only essential during the challenge phase for recall proliferation of memory CD8 T cells. Furthermore, we show that generation of proliferation-competent memory CD8 T cells is independent of CD40 and CCR5 and that in vivo IL-2 supplementation neither during priming nor during challenge was able to rescue recall proliferation of "unhelped" memory CD8 T cells.
authors.affiliation: Swiss Federal Institute of Technology, Institute for Microbiology, Wolfgang-Pauli-Strasse 10, Zurich, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Agnellini
authors.forename: Melanie
authors.initials: M
authors.lastname: Wiesel
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwarz
authors.forename: Petra
authors.initials: P
authors.lastname: Wolint
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
chemical_list: D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2