scholarly journals Requirements for Differentiation of an Immature CD4+8+T-Cell Line

1997 ◽  
Vol 5 (2) ◽  
pp. 91-103 ◽  
Author(s):  
Jenefer Dekoning ◽  
Jonathan G. Kaye
Keyword(s):  
Signal Transduction ◽  
Cell Differentiation ◽  
T Cell ◽  
Cell Line ◽  
T Cell Differentiation ◽  
Chain Molecule ◽  
Tcr Signal Transduction ◽  
Limited Function ◽  
Synergistic Response ◽  
Chimeric Molecules

The CD3ɛ and ζ chains of the TCR have been shown to possess independent signaling capabilities. Studies with chimeric molecules containing the cytoplasmic domains of either ζ or ɛ have suggested that these two structurally distinct members of the TCR-CD3 complex are able to function autonomously and have redundant features in the context of TCR-signal transduction in mature T cells. Expression of a chimeric human IL-2-receptor-ζ-chain molecule in the CD4+8+T-cell line, DPK, has enabled us to directly analyze responses initiated by the ζ-chain-signaling module alone within the context of immature T-cell differentiation. In this paper, we show that antibody crosslinking of the chimeric ζ chain delivers only a limited activation signal as measured by Ca[2+] flux, induction of low-level CD5 expression, and minimal differentiation as assessed by loss of cell-surface CD8 expression. TCR-induced activation through antibody crosslinking of the endogenous CD3ɛ receptor in the absence of costimulation was also relatively inefficient in initiating activation and differentiation. However, co-crosslinking of the CD4 coreceptor with CD3 resulted in a synergistic response, where as there was little effect of co-crosslinking of CD4 and the ζ-chain chimera. Striking differences were also observed in the substrate pattern of tyrosine phosphorylation, as well as lymphokine secretion following triggering through the intact TCR versus the ζ chain alone. These results indicate that although the ζ-chain may possess some signaling capacities similar to that of the intact TCR, it appears to have limited function as an autonomous subunit in initiating CD4+8+T-cell differentiation.

scholarly journals Ikaros Induces Quiescence and T-Cell Differentiation in a Leukemia Cell Line

2005 ◽  
Vol 25 (5) ◽  
pp. 1645-1654 ◽  
Author(s):  
Katie L. Kathrein ◽  
Rachelle Lorenz ◽  
Angela Minniti Innes ◽  
Erin Griffiths ◽  
Susan Winandy
Keyword(s):  
Cell Cycle ◽  
Cell Differentiation ◽  
T Cell ◽  
Tumor Suppressor ◽  
Cell Line ◽  
Tumor Suppressor Gene ◽  
Leukemia Cell ◽  
Suppressor Gene ◽  
T Cell Differentiation ◽  
Leukemia Cell Line

ABSTRACT Ikaros is a hematopoietic cell-specific zinc finger DNA binding protein that plays an important role in lymphocyte development. Genetic disruption of Ikaros results in T-cell transformation. Ikaros null mice develop leukemia with 100% penetrance. It has been hypothesized that Ikaros controls gene expression through its association with chromatin remodeling complexes. The development of leukemia in Ikaros null mice suggests that Ikaros has the characteristics of a tumor suppressor gene. In this report, we show that the introduction of Ikaros into an established mouse Ikaros null T leukemia cell line leads to growth arrest at the G0/G1 stage of the cell cycle. This arrest is associated with up-regulation of the cell cycle-dependent kinase inhibitor p27kip1, the induction of expression of T-cell differentiation markers, and a global and specific increase in histone H3 acetylation status. These studies provide strong evidence that Ikaros possesses the properties of a bona fide tumor suppressor gene for the T-cell lineage and offer insight into the mechanism of Ikaros's tumor suppressive activity.

scholarly journals T-cell differentiation of multipotent hematopoietic cell line EML in the OP9-DL1 coculture system

2009 ◽  
Vol 37 (8) ◽  
pp. 909-923.e1 ◽  
Author(s):  
Snježana Kutleša ◽  
Jennifer Zayas ◽  
Alexandra Valle ◽  
Robert B. Levy ◽  
Roland Jurecic
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Cell Line ◽  
T Cell Differentiation ◽  
Hematopoietic Cell ◽  
Hematopoietic Cell Line ◽  
Coculture System

Lmo2 Induces T-Cell Leukemia with Epigenetic Deregulation of CD4.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3361-3361
Author(s):  
Susan Cleveland ◽  
Utpal P. Dave
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Transgenic Mice ◽  
Cell Line ◽  
Trichostatin A ◽  
T Cell Differentiation ◽  
Transcriptional Level ◽  
Double Negative ◽  
Double Positive ◽  
Single Positive

Abstract The LIM domain Only-2 (Lmo2) oncogene is deregulated in the majority of human T-cell acute lymphoblastic leukemias (T-ALL). Enforced, constitutive expression of Lmo2 in transgenic mice using the T-cell-specific Cd2 promoter/enhancer induces T-ALL with median latency of 200 days and 100% penetrance. These transgenic mice have a pre-leukemic differentiation block at the double negative stage (CD4− CD8−) of T-cell differentiation. Despite this, T-ALLs in these mice arise from various stages of T-cell differentiation. To explore the relationship between T-cell development and Lmo2 oncogene function, we established cell lines from four independent T-cell tumors representing the double negative (DN), double positive (DP), and single positive (SP) stages. Two of the lines showed variegated expression of CD4 antigen. One line, 32080, was striking in that CD4 was expressed in 50% of cells whereas CD8 was uniformly present. The cell line expressed markers consistent with the intermediate single positive stage (ISP) to double positive (DP) stage transition. We sorted the 32080 line for highly CD4 positive and negative cells and observed them in culture. After one week, both sorted populations showed variegated CD4 expression. We determined CD4 expression was regulated at the transcriptional level and not due to post-transcriptional effects and that cell replication was necessary to re-establish CD4 variegation. Importantly, variegated CD4 expression was dependent on Lmo2 because its knockdown resulted in decreased CD4 expression. HDAC inhibition by trichostatin A had the reciprocal effect of inducing more CD4 expression suggesting that chromatin modification was playing a role. The CD4 locus was analyzed by chromatin immunoprecipitation and histone H3 methylation patterns consistent with silencing were found in the CD4 negative sorted cells but not in the CD4 positive population. The 32080 cell line is a striking model of ISP to DP T-cell plasticity and invokes a novel mechanism by which Lmo2 functions.

Electron microscope study of the secretory activity of epithelial cells in embryonic thymus

1990 ◽  
Vol 48 (3) ◽  
pp. 382-383
Author(s):  
H. Alasam
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Epithelial Cells ◽  
Electron Density ◽  
Secretory Activity ◽  
T Cell Differentiation ◽  
High Electron ◽  
Transmission Electron ◽  
Medullary Epithelial Cells ◽  
Thymic Factor

The possibility that intrathymic T-cell differentiation involves stem cell-lymphoid interactions in embryos led us to study the ultrastructure of epithelial cell in normal embryonic thymus. Studies in adult thymus showed that it produces several peptides that induce T-cell differentiation. Several of them have been chemically characterized, such as thymosin α 1, thymopoietin, thymic humoral factor or the serum thymic factor. It was suggested that most of these factors are secreted by populations of A and B-epithelial cells.Embryonic materials were obtained from inbred matings of Swiss Albino mice. Thymuses were disected from embryos 17 days old and prepared for transmission electron microscopy. Our studies showed that embryonic thymus at this stage contains undifferentiated and differentiated epithelial cells, large lymphoblasts, medium and few small lymphocytes (Fig. 5). No differences were found between cortical and medullary epithelial cells, in contrast to the findings of Van Vliet et al,. Epithelial cells were mostly of the A-type with low electron density in both cytoplasm and nucleus. However few B-type with high electron density were also found (Fig. 7).

Role of CD5 expression on TCRγδ T cell-differentiation and development of chronic intestinal inflammation

2001 ◽  
Vol 120 (5) ◽  
pp. A517-A517
Author(s):  
A MIZOGUCHI ◽  
E MIZOGUCHI ◽  
Y DEJONG ◽  
H TAKEDATSU ◽  
F PREFFER ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Intestinal Inflammation ◽  
T Cell Differentiation ◽  
Chronic Intestinal Inflammation
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