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PLoS One ; 8(7): e67821, 2013.
Article in English | MEDLINE | ID: mdl-23844100

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-ß, 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.


Subject(s)
CD4 Antigens/metabolism , CD8 Antigens/metabolism , Interferon-gamma/pharmacology , Interleukin-7/pharmacology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/metabolism , Transforming Growth Factor beta/pharmacology , Adoptive Transfer , Animals , Antigens, CD/genetics , Antigens, CD/metabolism , Antigens, Differentiation/genetics , Antigens, Differentiation/metabolism , CTLA-4 Antigen/genetics , CTLA-4 Antigen/metabolism , Cell Differentiation/drug effects , Cell Lineage/genetics , Core Binding Factor Alpha 3 Subunit/genetics , Core Binding Factor Alpha 3 Subunit/metabolism , Cytokines/biosynthesis , Immunophenotyping , Interferon-gamma/genetics , Intestinal Mucosa/immunology , Mice , Mice, Knockout , NK Cell Lectin-Like Receptor Subfamily K/genetics , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Programmed Cell Death 1 Receptor , T-Lymphocytes, Regulatory/cytology , T-Lymphocytes, Regulatory/immunology , Vitamin D/pharmacology , Lymphocyte Activation Gene 3 Protein
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