title: Memory CD4 T cells emerge from effector T-cell progenitors.
abstract: A hallmark of adaptive immunity is the generation of memory T cells that confer long-lived, antigen-specific protection against repeat challenges by pathogens. Understanding the mechanisms by which memory T cells arise is important for rational vaccination strategies and improved therapeutic interventions for chronic infections and autoimmune disorders. The large clonal expansion of CD8 T cells in response to some infections has made the development of CD8 T-cell memory more amenable to study, giving rise to a model of memory cell differentiation in which a fraction of fully competent effector T cells transition into long-lived memory T cells. Delineation of CD4 T-cell memory development has proved more difficult as a result of limitations on tracking the smaller populations of CD4 effector T cells generated during a pathogenic challenge, complicating efforts to determine whether CD4 memory T cells are direct descendants of effector T cells or whether they develop by alternative pathways. Here, using two complementary cytokine reporter mouse models to identify interferon (IFN)-gamma-positive effector T cells and track their fate, we show that the lineage relationship between effector and memory CD4 T cells resembles that for CD8 T cells responding to the same pathogen. We find that, in parallel with effector CD8 T cells, IFN-gamma-positive effector CD4 T cells give rise to long-lived memory T cells capable of anamnestic responses to antigenic rechallenge.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, 845 19th Street South, Birmingham, Alabama 35294, USA.
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Harrington
authors.forename: Karen M
authors.initials: KM
authors.lastname: Janowski
authors.forename: James R
authors.initials: JR
authors.lastname: Oliver
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Zajac
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019070:Cell Lineage; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D000941:Antigens; D007371:Interferon-gamma