title: IL-4 and IL-15 promotion of virtual memory CD8+T cells is determined by genetic background.
abstract: Virtual memory (VM) CD8+T cells are present in unimmunized mice, yet possess T-cell receptors specific for foreign antigens. To date, VM cells have only been characterized in C57BL/6 mice. Here, we assessed the cytokine requirements for VM cells in C57BL/6 and BALB/c mice. As reported previously, VM cells in C57BL/6 mice rely mostly on IL-15 and marginally on IL-4. In stark contrast, VM cells in BALB/c mice rely substantially on IL-4 and marginally on IL-15. Further, NKT cells are the likely source of IL-4, because CD1d-deficient mice on a BALB/c background have significantly fewer VM cells. Notably, this NKT/IL-4 axis contributes to appropriate effector and memory T-cell responses to infection in BALB/c mice, but not in C57BL/6 mice. However, the effects of IL-4 are manifest prior to, rather than during, infection. Thus, cytokine-mediated control of the precursor population affects the development of virus-specific CD8+T-cell memory. Depending upon the genetic background, different cytokines encountered before infection may influence the subsequent ability to mount primary and memory anti-viral CD8+T-cell responses.
authors.affiliation: Division of Immunobiology, Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Pulak
authors.initials: P
authors.lastname: Tripathi
authors.affiliation: Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.|Departments of Medicine and Research, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH, USA.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Morris
authors.affiliation: Division of Immunobiology, Children's Hospital Medical Center, Cincinnati, OH, USA.|Departments of Medicine and Research, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Perkins
authors.affiliation: Division of Immunobiology, Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Allyson
authors.initials: A
authors.lastname: Sholl
authors.affiliation: Division of Immunobiology, Children's Hospital Medical Center, Cincinnati, OH, USA. finkelfd@ucmail.uc.edu.|Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA. finkelfd@ucmail.uc.edu.|Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA. finkelfd@ucmail.uc.edu.|Departments of Medicine and Research, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH, USA. finkelfd@ucmail.uc.edu.
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.affiliation: Division of Immunobiology, Children's Hospital Medical Center, Cincinnati, OH, USA. David.Hildeman@cchmc.org.|Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA. David.Hildeman@cchmc.org.
authors.forename: David A
authors.initials: DA
authors.lastname: Hildeman
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics; D001117:Arenaviridae Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D007111:Immunity, Cellular / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology
chemical_list: D055610:Antigens, CD1d; D019409:Interleukin-15; D015847:Interleukin-4
keywords: CD122; Genetic background; IL-4; STAT6; T-cell memory