Simulation as an alternative to linear programming of human T-cell lymphotropic virus I (HTLV-I) model infection of CD4+ T-cells

2018 ◽  
Vol 13 (10) ◽  
pp. 455-471
Author(s):  
Mohammed Alabedalhadi
Keyword(s):  
T Cells ◽  
Linear Programming ◽  
T Cell ◽  
Cd4 T Cells ◽  
Human T Cell

The tumor marker Fascin is strongly induced by the Tax oncoprotein of HTLV-1 through NF-κB signals

Blood ◽  
2011 ◽  
Vol 117 (13) ◽  
pp. 3609-3612 ◽  
Author(s):  
Andrea K. Kress ◽  
Martina Kalmer ◽  
Aileen G. Rowan ◽  
Ralph Grassmann ◽  
Bernhard Fleckenstein
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Marker ◽  
Cd4 T Cells ◽  
Initial Step ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Viral Oncoprotein ◽  
Adult T Cell Leukemia ◽  
Human T Cell

AbstractOncogenic transformation of CD4+ T cells by human T-cell lymphotropic virus type 1 (HTLV-1) is understood as the initial step to adult T-cell leukemia/lymphoma, a process that is mainly initiated by perturbation of cellular signaling by the viral Tax oncoprotein, a potent transcriptional regulator. In search of novel biomarkers with relevance to oncogenesis, we identified the tumor marker and actin-bundling protein Fascin (FSCN1) to be specifically and strongly up-regulated in both HTLV-1–transformed and adult T-cell leukemia/lymphoma patient-derived CD4+ T cells. Fascin is important for migration and metastasis in various types of cancer. Here we report that a direct link can exist between a single viral oncoprotein and Fascin expression, as the viral oncoprotein Tax was sufficient to induce high levels of Fascin. Nuclear factor-κB signals were important for Tax-mediated transcriptional regulation of Fascin in T cells. This suggests that Fascin up-regulation by Tax contributes to the development of HTLV-1–associated pathogenesis.

scholarly journals Human T Cell Lymphotropic Virus Type I (HTLV-I)-Specific CD4+T Cells: Immunodominance Hierarchy and Preferential Infection with HTLV-I

2004 ◽  
Vol 172 (3) ◽  
pp. 1735-1743 ◽  
Author(s):  
Peter K. C. Goon ◽  
Tadahiko Igakura ◽  
Emmanuel Hanon ◽  
Angelina J. Mosley ◽  
Anna Barfield ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Cd4 T Cells ◽  
Type I ◽  
Human T Cell

scholarly journals Retrovirally induced CTL degranulation mediated by IL-15 expression and infection of mononuclear phagocytes in patients with HTLV-I–associated neurologic disease

Blood ◽  
2008 ◽  
Vol 112 (6) ◽  
pp. 2400-2410 ◽  
Author(s):  
Yoshimi Enose-Akahata ◽  
Unsong Oh ◽  
Christian Grant ◽  
Steven Jacobson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Spastic Paraparesis ◽  
Cd8 T Cell ◽  
Mononuclear Phagocytes ◽  
Type I ◽  
Human T Cell ◽  
Ifn Γ

AbstractCD8+ T cells contribute to central nervous system inflammation in human T-cell lymphotropic virus type I (HTLV-I)–associated myelopathy/tropical spastic paraparesis (HAM/TSP). We analyzed CD8+ T-cell dysfunction (degranulation and IFN-γ production) and have demonstrated that CD8+ T cells of patients with HAM/TSP (HAM/TSP patients) spontaneously degranulate and express IFN-γ in ex vivo unstimulated culture. CD8+ T cells of HTLV-I asymptomatic carriers and healthy donors did not. Spontaneous degranulation was detected in Tax11-19/HLA-A*201 tetramer+ cells, but not in CMV pp65 tetramer+ cells. Interestingly, degranulation and IFN-γ production in CD8+ T cells was induced by coculture with autologous CD14+ cells, but not CD4+ T cells, of HAM/TSP patients, which correlated with proviral DNA load in CD14+ cells of infected patients. Moreover, the expression of IL-15, which induced degranulation and IFN-γ production in infected patients, was enhanced on surface of CD14+ cells in HAM/TSP patients. Blockade of MHC class I and IL-15 confirmed these results. Thus, CD8+ T-cell dysregulation was mediated by both virus infection and enhanced IL-15 on CD14+ cells in HAM/TSP patients. Despite lower viral expression than in CD4+ T cells, HTLV-I–infected or –activated CD14+ cells may be a heretofore important but under recognized reservoir particularly in HAM/TSP patients.

scholarly journals Alpha and Lambda Interferon Together Mediate Suppression of CD4 T Cells Induced by Respiratory Syncytial Virus

2006 ◽  
Vol 80 (10) ◽  
pp. 5032-5040 ◽  
Author(s):  
Bo Chi ◽  
Harold L. Dickensheets ◽  
Kirsten M. Spann ◽  
Marc A. Alston ◽  
Cindy Luongo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Types ◽  
T Cell Proliferation ◽  
Live Virus ◽  
Human T Cell ◽  
Syncytial Virus

ABSTRACT The mechanism by which respiratory syncytial virus (RSV) suppresses T-cell proliferation to itself and other antigens is poorly understood. We used monocyte-derived dendritic cells (MDDC) and CD4 T cells and measured [3H]thymidine incorporation to determine the factors responsible for RSV-induced T-cell suppression. These two cell types were sufficient for RSV-induced suppression of T-cell proliferation in response to cytomegalovirus or Staphylococcus enterotoxin B. Suppressive activity was transferable with supernatants from RSV-infected MDDC and was not due to transfer of live virus or RSV F (fusion) protein. Supernatants from RSV-infected MDDC, but not MDDC exposed to UV-killed RSV or mock conditions, contained alpha interferon (IFN-α; median, 43 pg/ml) and IFN-λ (approximately 1 to 20 ng/ml). Neutralization of IFN-α with monoclonal antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-λ with MAb against either of its receptor chains, IFN-λR1 (interleukin 28R [IL-28R]) or IL-10R2, had a modest effect. In contrast, blocking the two receptors together markedly reduced or completely blocked the RSV-induced suppression of CD4 T-cell proliferation. Defining the mechanism of RSV-induced suppression may guide vaccine design and provide insight into previously uncharacterized human T-cell responses and activities of interferons.

scholarly journals GATA-3 in Human T Cell Helper Type 2 Development

2004 ◽  
Vol 199 (3) ◽  
pp. 423-428 ◽  
Author(s):  
Alla Skapenko ◽  
Jan Leipe ◽  
Uwe Niesner ◽  
Koen Devriendt ◽  
Rolf Beetz ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Differentiation ◽  
Mrna Levels ◽  
Effector Functions ◽  
Th2 Cell ◽  
Human T Cell

The delineation of the in vivo role of GATA-3 in human T cell differentiation is a critical step in the understanding of molecular mechanisms directing human immune responses. We examined T cell differentiation and T cell–mediated effector functions in individuals lacking one functional GATA-3 allele. CD4 T cells from GATA-3+/− individuals expressed significantly reduced levels of GATA-3, associated with markedly decreased T helper cell (Th)2 frequencies in vivo and in vitro. Moreover, Th2 cell–mediated effector functions, as assessed by serum levels of Th2-dependent immunoglobulins (Igs; IgG4, IgE), were dramatically decreased, whereas the Th1-dependent IgG1 was elevated compared with GATA-3+/+ controls. Concordant with these data, silencing of GATA-3 in GATA-3+/+ CD4 T cells with small interfering RNA significantly reduced Th2 cell differentiation. Moreover, GATA-3 mRNA levels increased under Th2-inducing conditions and decreased under Th1-inducing conditions. Taken together, the data strongly suggest that GATA-3 is an important transcription factor in regulating human Th2 cell differentiation in vivo.

scholarly journals Dynamics of human T-cell lymphotropic virus I (HTLV-I) infection of CD4+ T-cells

2004 ◽  
Vol 327 (11) ◽  
pp. 1009-1016 ◽  
Author(s):  
Patricia Katri ◽  
Shigui Ruan
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Human T Cell

scholarly journals Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells

Blood ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 2994-3003 ◽  
Author(s):  
Alison Y. Swaims ◽  
Francesca Khani ◽  
Yingyu Zhang ◽  
Arthur I. Roberts ◽  
Satish Devadas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Activation ◽  
Cd4 T Cells ◽  
Leukemia Virus ◽  
Host Immune System ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Immune System Activation ◽  
Human T Cell

AbstractInfection with the human T-cell leukemia virus-1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia/lymphoma (ATL). Although the pathogenesis of these disorders is poorly understood, it involves complex interactions with the host immune system. Activation of infected T cells may play an important role in disease pathogenesis through induction of the oncogenic HTLV-1 Tax transactivator protein. To test this hypothesis, we employed transgenic mice in which Tax is regulated by the HTLV-1 LTR. T-cell receptor stimulation of LTR-Tax CD4+ T cells induced Tax expression, hyper-proliferation, and immortalization in culture. The transition to cellular immortalization was accompanied by markedly increased expression of the antiapoptotic gene, mcl-1, previously implicated as important in T-cell survival. Immortalized cells exhibited a CD4+CD25+CD3− phenotype commonly observed in ATL. Engraftment of activated LTR-Tax CD4+ T cells into NOD/Shi-scid/IL-2Rγ null mice resulted in a leukemia-like phenotype with expansion and tissue infiltration of Tax+, CD4+ lymphocytes. We suggest that immune activation of infected CD4+ T cells plays an important role in the induction of Tax expression, T-cell proliferation, and pathogenesis of ATL in HTLV-1–infected individuals.

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