Immortalized dendritic like cell lines derived from mice lacking both type I and type II interferon receptors, process and present MHC II restricted antigen to primed and naive T cells, induce MLR and support virus replication

The human T-cell- or lymphocyte-specific gene, lck, encodes a tyrosine kinase and is a member of the src family. In this report we demonstrate that there are two classes of human lck transcripts (types I and II), containing different 5'-untranslated regions, which are expressed from two distinct promoters. No apparent sequence similarity was observed between the 5'-flanking regions of the two promoters. The expression of lck in human T-cell leukemia and carcinoma cell lines and in human peripheral blood T lymphocytes was examined by S1 nuclease and primer extension mapping and by Northern (RNA) blot analysis of total cellular RNA. The following results were obtained. (i) Two RNA start sites in the downstream promoter were used to generate type I transcripts. (ii) The major human type I start site has not been described for the mouse. (iii) At least five RNA start sites in the upstream promoter were used to generate type II transcripts. (iv) In T cells and in two colon carcinoma cell lines, type II transcripts were present in higher amounts than type I transcripts. (v) In T cells treated with phytohemagglutinin, tetradecanoylphorbol acetate, and cyclosporin A, the modulation of lck expression was associated primarily with changes in levels of type II transcripts. The above results suggest that the two human lck promoters are utilized differentially and may be regulated independently during certain physiological states.

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F.126. Glatiramer Acetate-induced Human Type II Monocytes Influence Differentiation of Naïve T Cells

Clinical Immunology ◽

10.1016/j.clim.2009.03.377 ◽

2009 ◽

Vol 131 ◽

pp. S127-S128

Author(s):

Collin Spencer ◽

Martin Weber ◽

Thomas Prod'homme ◽

Scott Zamvil

Keyword(s):

T Cells ◽

Glatiramer Acetate ◽

Type Ii ◽

Naive T Cells ◽

Naïve T Cells ◽

Human Type

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T–cell proliferation in vivo and the role of cytokines

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2000.0568 ◽

2000 ◽

Vol 355 (1395) ◽

pp. 317-322 ◽

Cited By ~ 42

Author(s):

Jonathan Sprent ◽

Xiaohong Zhang ◽

Siquan Sun ◽

David Tough

Keyword(s):

T Cells ◽

Specific Antigen ◽

Type I ◽

Experimental Conditions ◽

Naive T Cells ◽

Memory Phenotype ◽

Naïve T Cells ◽

Polycytidylic Acid ◽

Effector Cytokines

Unlike typical naive T cells, T cells with an activated (CD44 hi ) memory phenotype show a rapid rate of proliferation in vivo . The turnover of memory–phenotype CD8 + T cells can be considerably augmented by injecting mice with various compounds, including polyinosinic–polycytidylic acid, lipopolysaccharide and immunostimulatory DNA (CpG DNA). Certain cytokines, notably type I (α, β) interferons (IFNI), have a similar effect. These agents appear to induce proliferation of CD44 hi CD8 + cells in vivo by an indirect process involving production of effector cytokines, possibly interleukin–15, by antigen–presenting cells. Although none of the agents tested induces proliferation of naive–phenotype T cells, IFN–I has the capacity to cause upregulation of surface markers on purified naive T cells. Depending upon the experimental conditions used, IFN–I can either inhibit or enhance primary responses of naive T cells to specific antigen.

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Structure of the two promoters of the human lck gene: differential accumulation of two classes of lck transcripts in T cells.

Molecular and Cellular Biology ◽

10.1128/mcb.9.5.2173 ◽

1989 ◽

Vol 9 (5) ◽

pp. 2173-2180 ◽

Cited By ~ 32

Author(s):

T Takadera ◽

S Leung ◽

A Gernone ◽

Y Koga ◽

Y Takihara ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Lines ◽

Carcinoma Cell ◽

Human Peripheral Blood ◽

Specific Gene ◽

Type I ◽

Type Ii ◽

Carcinoma Cell Lines ◽

Human T Cell

The human T-cell- or lymphocyte-specific gene, lck, encodes a tyrosine kinase and is a member of the src family. In this report we demonstrate that there are two classes of human lck transcripts (types I and II), containing different 5'-untranslated regions, which are expressed from two distinct promoters. No apparent sequence similarity was observed between the 5'-flanking regions of the two promoters. The expression of lck in human T-cell leukemia and carcinoma cell lines and in human peripheral blood T lymphocytes was examined by S1 nuclease and primer extension mapping and by Northern (RNA) blot analysis of total cellular RNA. The following results were obtained. (i) Two RNA start sites in the downstream promoter were used to generate type I transcripts. (ii) The major human type I start site has not been described for the mouse. (iii) At least five RNA start sites in the upstream promoter were used to generate type II transcripts. (iv) In T cells and in two colon carcinoma cell lines, type II transcripts were present in higher amounts than type I transcripts. (v) In T cells treated with phytohemagglutinin, tetradecanoylphorbol acetate, and cyclosporin A, the modulation of lck expression was associated primarily with changes in levels of type II transcripts. The above results suggest that the two human lck promoters are utilized differentially and may be regulated independently during certain physiological states.

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Interferon-producing Cells Fail to Induce Proliferation of Naive T Cells but Can Promote Expansion and T Helper 1 Differentiation of Antigen-experienced Unpolarized T Cells

Journal of Experimental Medicine ◽

10.1084/jem.20021091 ◽

2003 ◽

Vol 197 (7) ◽

pp. 899-906 ◽

Cited By ~ 127

Author(s):

Anne Krug ◽

Ravi Veeraswamy ◽

Andrew Pekosz ◽

Osami Kanagawa ◽

Emil R. Unanue ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Mhc Class Ii ◽

Type I ◽

T Helper ◽

T Helper 1 ◽

Naive T Cells ◽

Naïve T Cells ◽

Antigen Presenting

Interferon-producing cells (IPCs) secrete high levels of type I interferon in response to certain viruses. The lack of lineage markers, the expression of major histocompatibility complex (MHC) class II and the capacity to stimulate allogeneic T cells have led these cells to be classified as a subset of dendritic cells (DCs), called plasmacytoid DCs (PDCs). However, the role of IPCs/PDCs in initiating primary immune responses remains elusive. Here we examined the antigen presenting capacity of murine IPCs in antigen specific systems. While CD8α+ and CD11b+ DCs induced logarithmic expansion of naive CD4 and CD8 T cells, without conferring T helper commitment at a first encounter, primary IPCs lacked the ability to stimulate naive T cells. However, when antigen-experienced, nonpolarized T cells expanded by classical DC subsets, were restimulated by IPCs, they proliferated and produced high amounts of IFN-γ. These data indicate that IPCs can effectively stimulate preactivated or memory-type T cells and exert an immune-regulatory role. They also suggest that expansion of naive T cells and acquisition of effector function during antigen-specific T cell responses may involve different antigen-presenting cell (APC) types. Independent and coordinated control of T cell proliferation and differentiation would provide the immune system with greater flexibility in regulating immune responses.

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The Envelope Gene of Transmitted HIV-1 Resists a Late Interferon Gamma-Induced Block

Journal of Virology ◽

10.1128/jvi.02254-16 ◽

2017 ◽

Vol 91 (7) ◽

Cited By ~ 17

Author(s):

Suzannah J. Rihn ◽

Toshana L. Foster ◽

Idoia Busnadiego ◽

Muhamad Afiq Aziz ◽

Joseph Hughes ◽

...

Keyword(s):

T Cells ◽

Cell Lines ◽

Type I Interferon ◽

Single Amino Acid ◽

Envelope Gene ◽

Type I ◽

Type Ii ◽

Antiviral State ◽

Ifn Γ ◽

Hiv 1

ABSTRACT Type I interferon (IFN) signaling engenders an antiviral state that likely plays an important role in constraining HIV-1 transmission and contributes to defining subsequent AIDS pathogenesis. Type II IFN (IFN-γ) also induces an antiviral state but is often primarily considered to be an immunomodulatory cytokine. We report that IFN-γ stimulation can induce an antiviral state that can be both distinct from that of type I interferon and can potently inhibit HIV-1 in primary CD4+ T cells and a number of human cell lines. Strikingly, we find that transmitted/founder (TF) HIV-1 viruses can resist a late block that is induced by type II IFN, and the use of chimeric IFN-γ-sensitive/resistant viruses indicates that interferon resistance maps to the env gene. Simultaneously, in vitro evolution also revealed that just a single amino acid substitution in the envelope can confer substantial resistance to IFN-mediated inhibition. Thus, the env gene of transmitted HIV-1 confers resistance to a late block that is phenotypically distinct from blocks previously described to be resisted by env and is therefore mediated by unknown IFN-γ-stimulated factor(s) in human CD4+ T cells and cell lines. This important unidentified block could play a key role in constraining HIV-1 transmission. IMPORTANCE The human immune system can hinder invading pathogens through interferon (IFN) signaling. One consequence of this signaling is that cells enter an antiviral state, increasing the levels of hundreds of defenses that can inhibit the replication and spread of viruses. The majority of HIV-1 infections result from a single virus particle (the transmitted/founder) that makes it past these defenses and colonizes the host. Thus, the founder virus is hypothesized to be a relatively interferon-resistant entity. Here, we show that certain HIV-1 envelope genes have the unanticipated ability to resist specific human defenses mediated by different types of interferons. Strikingly, the envelope gene from a founder HIV-1 virus is far better at evading these defenses than the corresponding gene from a common HIV-1 lab strain. Thus, these defenses could play a role in constraining the transmission of HIV-1 and may select for transmitted viruses that are resistant to this IFN-mediated inhibition.

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