title: Autocrine IL-2 is required for secondary population expansion of CD8(+) memory T cells.
abstract: Two competing theories have been put forward to explain the role of CD4(+) T cells in priming CD8(+) memory T cells: one proposes paracrine secretion of interleukin 2 (IL-2); the other proposes the activation of antigen-presenting cells (APCs) via the costimulatory molecule CD40 and its ligand CD40L. We investigated the requirement for IL-2 by the relevant three cell types in vivo and found that CD8(+) T cells, rather than CD4(+) T cells or dendritic cells (DCs), produced the IL-2 necessary for CD8(+) T cell memory. Il2(-/-) CD4(+) T cells were able to provide help only if their ability to transmit signals via CD40L was intact. Our findings reconcile contradictory elements implicit in each model noted above by showing that CD4(+) T cells activate APCs through a CD40L-dependent mechanism to enable autocrine production of IL-2 in CD8(+) memory T cells.
authors.affiliation: Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Feau
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.forename: Susan
authors.initials: S
authors.lastname: Togher
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000254:growth & development; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D007376:Interleukin-2; D023201:CD40 Ligand