title: In vitro induction of regulatory CD4+CD8α+ T cells by TGF-β, IL-7 and IFN-γ.
abstract: In vitro CD4(+) T cell differentiation systems have made important contributions to understanding the mechanisms underlying the differentiation of naive CD4(+) T cells into effector cells with distinct biological functions. Mature CD4(+) T cells expressing CD8αα homodimers are primarily found in the intestinal mucosa of men and mice, and to a lesser extent in other tissues such as peripheral blood. Although CD4(+)CD8α(+) T cells are easily identified, very little is known about their development and immunological functions. It has been reported, however, that CD4(+)CD8α(+) T cells possess regulatory properties. In this report, we present a novel in vitro differentiation system where CD4(+) T cells are stimulated to become CD4(+)CD8α(+) T cells in the presence of TGF-β, IL-7 and IFN-γ, resulting in cells with very similar features as CD4(+)CD8α(+) intraepithelial lymphocytes. This novel in vitro differentiation culture should provide a powerful and tractable tool for dissecting the differentiation and biological functions of CD4(+)CD8α(+) T cells.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. luc.van.kaer@vanderbilt.edu
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Whitney A S
authors.initials: WA
authors.lastname: Rabacal
authors.forename: Holly M
authors.initials: HM
authors.lastname: Scott Algood
authors.forename: Vrajesh V
authors.initials: VV
authors.lastname: Parekh
authors.forename: Danyvid
authors.initials: D
authors.lastname: Olivares-Villagómez
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000235:genetics; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014807:Vitamin D / Q000494:pharmacology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D016827:CD8 Antigens; D060908:CTLA-4 Antigen; D050677:Core Binding Factor Alpha 3 Subunit; D016207:Cytokines; D015851:Interleukin-7; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta; D014807:Vitamin D; D007371:Interferon-gamma; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse