title: A self-help program for memory CD8+ T cells: positive feedback via CD40-CD40L signaling as a critical determinant of secondary expansion.
abstract: The ability of memory CD8+ T cells to rapidly proliferate and acquire cytolytic activity is critical for protective immunity against intracellular pathogens. The signals that control this recall response remain unclear. We show that CD40L production by memory CD8+ T cells themselves is an essential catalyst for secondary expansion when systemic inflammation is limited. Secondary immunization accompanied by high levels of systemic inflammation results in CD8+ T cell secondary expansion independent of CD4+ T cells and CD40-CD40L signaling. Conversely, when the inflammatory response is limited, memory CD8+ T cell secondary expansion requires CD40L-producing cells, and memory CD8+ T cells can provide this signal. These results demonstrate that vaccination regimens differ in their dependence on CD40L-expressing CD8+ T cells for secondary expansion, and propose that CD40L-expression by CD8+ T cells is a fail-safe mechanism that can promote memory CD8+ T cell secondary expansion when inflammation is limited.
authors.affiliation: Earle A. Chiles Research Institute, Robert W Franz Cancer Research Center, Providence Cancer Center, Portland, Oregon, United States of America.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Shugart
authors.forename: Shelly
authors.initials: S
authors.lastname: Bambina
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: Alice
authors.forename: Ryan
authors.initials: R
authors.lastname: Montler
authors.forename: Keith S
authors.initials: KS
authors.lastname: Bahjat
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001428:Bacterial Vaccines; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D025461:Feedback, Physiological; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000187:drug effects / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination; D014616:Vaccinia virus / Q000276:immunology; D014765:Viral Vaccines
chemical_list: D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines; D019013:CD40 Antigens; D014765:Viral Vaccines; D023201:CD40 Ligand; D000667:Ampicillin