title: Increased peripheral IL-4 leads to an expanded virtual memory CD8+ population.
abstract: Memory-phenotype CD8(+) T cells can arise even in the absence of overt Ag stimulation. Virtual memory (VM) CD8(+) T cells are CD8(+) T cells that develop a memory phenotype in the periphery of wild-type mice in an IL-15-dependent manner. Innate CD8(+) T cells, in contrast, are memory-phenotype CD8(+) T cells that develop in the thymus in response to elevated thymic IL-4. It is not clear whether VM cells and innate CD8(+) T cells represent two independent T cell lineages or whether they arise through similar processes. In this study, we use mice deficient in Nedd4-family interacting protein 1 to show that overproduction of IL-4 in the periphery leads to an expanded VM population. Nedd4-family interacting protein 1(-/-) CD4(+) T cells produce large amounts of IL-4 due to a defect in JunB degradation. This IL-4 induces a memory-like phenotype in peripheral CD8(+) T cells that includes elevated expression of CD44, CD122, and Eomesodermin and decreased expression of CD49d. Thus, our data show that excess peripheral IL-4 is sufficient to cause an increase in the VM population. Our results suggest that VM and innate CD8(+) T cells may be more similar than previously appreciated.
authors.affiliation: Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; and.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Kurzweil
authors.affiliation: Cell Pathology Division, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Ami
authors.initials: A
authors.lastname: LaRoche
authors.affiliation: Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; and Cell Pathology Division, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104 paulao@mail.med.upenn.edu.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Oliver
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000502:physiology*; D039441:Integrin alpha4 / Q000235:genetics / Q000276:immunology; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: C476399:Cd44 protein, mouse; C491198:Eomes protein, mouse; D018960:Hyaluronan Receptors; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; C584097:JunB protein, mouse; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D039441:Integrin alpha4; D015847:Interleukin-4