title: Flexibility accompanies commitment of memory CD4 lymphocytes derived from IL-4 locus-activated precursors.
abstract: Differentiation of T helper (Th) subset 2 effector lymphocytes is thought to foreclose on IFN-gamma gene expression. Using an IL-4 locus modified to detect transcriptional induction of this effector cytokine gene in developing Th2 cells, we show here that these cells contributed effectively to a long-term memory population. A memory CD4 subset formed efficiently from an activated population after transcriptional induction of the IL-4 locus and differentiation into an IL-4-producing subset with Th2 characteristics. Memory lymphocytes derived from Th2 cells with IL-4 locus activation remained committed to transcriptional competence of Th2 cytokine genes when reactivated and cultured under strong Th1-polarizing conditions. This commitment to transcriptional competence at Th2 cytokine gene loci upon recall activation indicates that linear differentiation is a substantial component of type 2 memory. Strikingly, however, descendants of the Th2 population could turn on IFN-gamma expression when reactivated after a quiescent period, revealing an unexpected flexibility allowing activation of the forbidden IFN-gamma gene after reactivation and growth.
authors.affiliation: Department of Microbiology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Adeeku
authors.forename: Prathyusha
authors.initials: P
authors.lastname: Gudapati
authors.forename: Yanice
authors.initials: Y
authors.lastname: Mendez-Fernandez
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Mark
authors.initials: M
authors.lastname: Boothby
mesh_terms: D019264:Adoptive Transfer; D000483:Alleles; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D007371:Interferon-gamma