scholarly journals The human OX40/gp34 system directly mediates adhesion of activated T cells to vascular endothelial cells.

1996 ◽  
Vol 183 (5) ◽  
pp. 2185-2195 ◽  
Author(s):  
A Imura ◽  
T Hori ◽  
K Imada ◽  
T Ishikawa ◽  
Y Tanaka ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Cell Leukemia ◽  
Activated T Cells ◽  
T Cell Lines

Fresh leukemic cells from patients with adult T cell leukemia (ATL) and some ATL-derived T cell lines show adhesion to human umbilical vein endothelial cells (HUVECs) mainly through E-selectin, but a proportion of this binding remains unaffected by the addition of combinations of antibodies against known adhesion molecules. By immunizing mice with one of such cell lines, we established monoclonal antibodies (mAbs), termed 131 and 315, that recognize a single cell surface antigen (Ag) and inhibit the remaining pathway of the adhesion. These mAbs did not react with normal resting peripheral blood mononuclear cells (PBMC) or most of the cell lines tested except for two other human T cell leukemia virus type I (HTLV-I)-infected T cell lines. After stimulation with phytohemagglutinin (PHA), PBMC expressed Ag 131/315 transiently, indicating that these mAbs define a T cell activation Ag. Western blotting and immunoprecipitation revealed that Ag 131/315 has an apparent molecular mass of 50 kD. Expression cloning was done by transient expression in COS-7 cells and immunological selection to isolate a cDNA clone encoding Ag 131/315. Sequence analysis of the cDNA indicated that it is identical to human OX40, a member of the tumor necrosis factor/nerve growth factor receptor family. We then found that gp34, the ligand of OX40, was expressed on HUVECs and other types of vascular endothelial cells. Furthermore, it was shown that the adhesion of CD4+ cells of PHA-stimulated PBMC to unstimulated HUVECs was considerably inhibited by either 131 or 315. Finally, OX40 transfectants of Kit 225, a human interleukin 2-dependent T cell line, were bound specifically to gp34 transfectants of MMCE, a mouse epithelial cell line, and this binding was blocked by either 315 or 5A8, an anti-gp34 mAb. These results indicate that the OX40/gp34 system directly mediates adhesion of activated T cells or OX40+-transformed T cells to vascular endothelial cells.

Human vascular endothelial cells process and present autoantigen to human T cell lines

1995 ◽  
Vol 7 (3) ◽  
pp. 471-479 ◽  
Author(s):  
Caroline O. S. Savage ◽  
Christopher J. Brooks ◽  
Gillian C. Harcourt ◽  
Jean K. Picard ◽  
William King ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Cell Lines ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Human T Cell ◽  
T Cell Lines

scholarly journals Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-I.

1983 ◽  
Vol 158 (6) ◽  
pp. 2024-2039 ◽  
Author(s):  
M Howard ◽  
L Matis ◽  
T R Malek ◽  
E Shevach ◽  
W Kell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Interleukin 2 ◽  
Activated T Lymphocytes ◽  
T Cell Lines ◽  
Activated B Cells

Antigen-activated T lymphocytes produce within 24 h of stimulation a factor that is indistinguishable biochemically and functionally from the B cell co-stimulating growth factor, BCGF-I, originally identified in induced EL4 supernatants: Supernatants from antigen-stimulated T cell lines are not directly mitogenic for resting B cells, but synergize in an H-2-unrestricted manner with anti-Ig activated B cells to produce polyclonal proliferation but not antibody-forming-cell development; biochemical studies reveal the B cell co-stimulating factor present in antigen-stimulated T cell line supernatants is identical by phenyl Sepharose chromatography and isoelectric focusing (IEF) to EL4 supernatant BCGF-I. We thus conclude that normal T cells produce BCGF-I in response to antigenic stimulation. Analysis of the mechanism of BCGF-I production by antigen-stimulated T cells showed that optimum amounts of BCGF-I were obtained as quickly as 24 h post-stimulation, and that the factor producing cells in the T cell line investigated bore the Lyt-1+2- phenotype. As few as 10(4) T cells produced sufficient BCGF-I to support the proliferation of 5 X 10(4) purified anti-Ig activated B cells. Finally, the activation of normal T cell lines to produce BCGF-I required either antigen presented in the context of syngeneic antigen-presenting cells (APC) or interleukin 2 (IL-2).

scholarly journals T cell growth factor receptors. Quantitation, specificity, and biological relevance

1981 ◽  
Vol 154 (5) ◽  
pp. 1455-1474 ◽  
Author(s):  
RJ Robb ◽  
A Munck ◽  
KA Smith
Keyword(s):  
T Cells ◽  
T Cell ◽  
Growth Factor ◽  
Cell Lines ◽  
Binding Sites ◽  
Activated T Cells ◽  
Receptor Sites ◽  
Polypeptide Hormones ◽  
T Cell Lines ◽  
T Cell Growth Factor

To examine directly the hypothesis that T cell growth factor (TCGF) interacts with target cells in a fashion similar to polypeptide hormones, the binding of radiolabeled TCGF to various cell populations was investigated. The results indicate that TCGF interacts with activated T cells via a receptor through which it initiates the T cell proliferative response. Internally radiolabeled TCGF, prepared from a human T leukemia cell line and purified by gel filtration and isoelectric focusing, retained biological activity and was uniform with respect to size and charge. Binding of radiolabeled TCGF to TCGF-dependent cytolytic T cells occurred rapidly (within 15 rain at 37 degrees C) and was both saturable and largely reversible. In addition, at 37 degrees C, a receptor- and lysosome-dependent degradation of TCGF occurred. Radiolabeled TCGF binding was specific for activated, TCGF-responsive T cells. Whereas unstimulated lymphocytes of human or murine origin and lipopolysaccharide-activated B cell blasts expressed few if any detectable binding sites, lectin- or alloantigen-activated cells had easily detectable binding sites. Moreover, compared with lectin- or alloantigen-activated T cells, long-term TCGF-dependent cytolytic and helper T cell lines and TCGF-dependent neo-plastic T cell lines bound TCGF with a similar affinity (dissociation constant of 5-25 pM) and expressed a similar number of receptor sites per cell (5,000-15,000). In contrast, a number of TCGF-independent cell lines of T cell, B cell, or myeloid origin did not bind detectable quantities of radiolabeled TCGF. Binding of radiolabeled TCGF to TCGF-responsive cells was specific, in that among several growth factors and polypeptide hormones tested, only TCGF competed for binding. Finally, the relative magnitude of T cell proliferation induced by a given concentration of TCGF closely paralleled the fraction of occupied receptor sites. As the extent of T cell clonal expansion depends on TCGF and on the TCGF receptor, the dissection of the molecular events surrounding the interaction of TCGF and its receptor that these studies permit, should provide new insight into the hormonelike regulation of the immune response by this lymphokine.

scholarly journals Aberrant Activation of the Interleukin-2 Autocrine Loop through the Nuclear Factor of Activated T Cells by Nonleukemogenic Human T-Cell Leukemia Virus Type 2 but Not by Leukemogenic Type 1 Virus

2005 ◽  
Vol 79 (18) ◽  
pp. 11925-11934 ◽  
Author(s):  
Akiko Niinuma ◽  
Masaya Higuchi ◽  
Masahiko Takahashi ◽  
Masayasu Oie ◽  
Yuetsu Tanaka ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Activated T Cells ◽  
Cell Leukemia Virus Type ◽  
Autocrine Loop ◽  
Human T Cell ◽  
T Cell Lines

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) but not HTLV-2 is associated with adult T-cell leukemia. We found that HTLV-2 Tax2 protein stimulated reporter gene expression regulated by the interleukin (IL)-2 promoter through the nuclear factor of activated T cells (NFAT) in a human T-cell line (Jurkat). However, the activity of HTLV-1 Tax1 was minimal in this system. T-cell lines immortalized by HTLV-2 but not HTLV-1 constitutively exhibited activated NFAT in the nucleus and constitutively expressed IL-2 mRNA. Cyclosporine A, an inhibitor of NFAT activation, abrogated the induction of IL-2 mRNA in HTLV-2-immortalized T-cell lines and concomitantly inhibited cell growth. This growth inhibition was rescued by the addition of IL-2 to the culture. Furthermore, anti-IL-2 receptor antibodies significantly reduced the proliferation of HTLV-2-infected T-cell lines but not that of HTLV-1-infected cells. Our results suggest that Tax2 activates an IL-2 autocrine loop mediated through NFAT that supports the growth of HTLV-2-infected cells under low-IL-2 conditions. This mechanism would be especially important in vivo, where this autocrine mechanism establishes a nonleukemogenic life-long HTLV-2 infection. The results also suggest that differences in long-term cytokine production between HTLV-1 and HTLV-2 infection are another factor for the differences in pathogenesis.

scholarly journals Failure of regulation of Tac antigen/TCGF receptor on adult T-cell leukemia cells by anti-Tac monoclonal antibody

Blood ◽  
1983 ◽  
Vol 61 (5) ◽  
pp. 1014-1016
Author(s):  
M Tsudo ◽  
T Uchiyama ◽  
H Uchino ◽  
J Yodoi
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Leukemic Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Down Regulation ◽  
Adult T Cell Leukemia ◽  
T Cell Lines

Anti-Tac monoclonal antibody, which blocks the membrane binding and action of human T-cell growth factor (TCGF), is strongly proposed to recognize TCGF receptor. We have demonstrated that anti-Tac antibody reacted with leukemic cells from patients with adult T-cell leukemia (ATL) and reacted with T-cell lines established from ATL cells. Although antigenic modulation, or down-regulation, of Tac antigen on activated normal T cells was induced by anti-Tac antibody, the expression of Tac antigen on ATL cells or T-cell lines was not affected when examined by the fluorescence-activated cell sorter (FACS) and the radioassay using 125I-staphylococcal protein A. These results indicate that regulation of Tac antigen-TCGF receptor is different between normal and malignant T cells, suggesting that failure of down- regulation of Tac antigen on leukemic cells by anti-Tac antibody may play an important role in the malignant proliferation of ATL cells.

scholarly journals RASGRP2 Suppresses Apoptosis via Inhibition of ROS Production in Vascular Endothelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Takuma Sato ◽  
Jun-ichi Takino ◽  
Kentaro Nagamine ◽  
Kazuto Nishio ◽  
Takamitsu Hori
Keyword(s):  
Endothelial Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
Ros Production ◽  
Overexpressing Cell ◽  
The Difference ◽  
Umbilical Vein Endothelial Cells

We have identified ras guanyl releasing protein 2 (rasgrp2) as a blood vessel related gene from Xenopus embryo. In addition, we reported that RASGRP2 is also expressed in human umbilical vein endothelial cells (HUVEC). It is known that RASGRP2 activates Ras-related protein 1 (Rap1). However, the function of RASGRP2 in human vascular endothelium remains unknown. Therefore, we performed functional analysis of RASGRP2 using immortalized HUVEC (TERT HUVEC). We established a stable RASGRP2 overexpressing cell line (TERT HUVEC R) and mock cell line (mock). Furthermore, we compared the activity of Rap1 and the generation of intracellular reactive oxygen species (ROS), which is related to cell death, in both cell lines. Significant increase in Rap1 activity was observed in the TERT HUVEC R compared to the mock. Furthermore, apoptosis by tumor necrosis factor-α (TNF-α) stimulation was significantly more reduced in the TERT HUVEC R than in the mock. In the mock, apoptosis induced by TNF-α stimulation was decreased by pretreatment with diphenyleneiodonium (DPI), which is an inhibitor of NADPH oxidase (NOX). However, in the TERT HUVEC R, apoptosis induced by TNF-α stimulation was not reduced after pretreatment of DPI. Furthermore, there was no reduction in ROS production in the TERT HUVEC R after DPI pretreatment. In addition, the difference in the degree of apoptosis induced by TNF-α stimulation in both cell lines was consistent with the difference in ROS production in the cell lines. From these results, it was suggested that RASGRP2 activates Rap1 and the activated Rap1 suppresses apoptosis via NOX inhibition.

Regulation of MHC class II expression in human T-cell malignancies

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1438-1444 ◽  
Author(s):  
Tjadine M. Holling ◽  
Erik Schooten ◽  
Anton W. Langerak ◽  
Peter J. van den Elsen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Mhc Class Ii ◽  
Lymphoblastic Leukemia ◽  
Class Ii ◽  
Activated T Cells ◽  
Prolymphocytic Leukemia ◽  
Human T Cell ◽  
T Cell Lines

Abstract Expression of major histocompatibility complex (MHC) class II molecules in human activated T cells is under normal circumstances regulated exclusively by the CIITA-PIII subtype of the class II transactivator (CIITA). In this study, we show that the absence of MHC class II expression in leukemic T cells was due to a lack of expression of CIITA, whereas in T-lymphoma cells, expression of CIITA correlated with expression of MHC class II. Interestingly, activation of a CIITA-promoter (P)III–reporter construct was not affected in leukemic T cells. This revealed that the absence of endogenous CIITA expression was not caused by a lack of transcription factors critical for CIITA-PIII activation but suggests the involvement of an epigenetic silencing mechanism. Subsequent analysis showed that the lack of human leukocyte antigen–DR (HLA-DR) expression correlated with hypermethylation of CIITA-PIII in leukemic T-cell lines and in primary T-cell acute lymphoblastic leukemia (T-ALL) and a T-cell prolymphocytic leukemia (T-PLL). Treatment of leukemic T-cell lines with a demethylation agent showed re-expression of CIITA-PIII and HLA-DRA. Furthermore, in vitro methylation of CIITA-PIII and subsequent assessment of CIITA-PIII activity in Jurkat leukemic T cells resulted in reduction of constitutive and CREB-1 (cyclic adenosine monophosphate [cAMP]–response element binding protein 1)–induced promoter activity. Together, these results argue for an important role of DNA hyper-methylation in the control of CIITA expression in leukemic T cells.

Overexpression of caveolin-1 in adult T-cell leukemia

Blood ◽  
2010 ◽  
Vol 115 (11) ◽  
pp. 2220-2230 ◽  
Author(s):  
Shigeki Sawada ◽  
Chie Ishikawa ◽  
Hiroe Tanji ◽  
Sawako Nakachi ◽  
Masachika Senba ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Signal Pathways ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Caveolin 1 ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
T Cell Lines

AbstractCaveolin-1 is implicated in the regulation of signal pathways. Adult T-cell leukemia (ATL) is a T-cell malignancy causatively associated with human T-cell leukemia virus type 1 (HTLV-1). To determine the role of caveolin-1 in leukemogenesis, we examined caveolin-1 expression levels in HTLV-1–infected T-cell lines and ATL cells. These cells expressed high levels of caveolin-1 compared with uninfected T-cell lines and normal peripheral blood mononuclear cells (PBMCs). Caveolin-1–positive ATL cells were detected in ATL lymph nodes and skin lesions, and caveolin-1 was also detected in the plasma of patients with ATL. Infection of a human T-cell line, an epithelial cell line, and normal PBMCs with HTLV-1 induced caveolin-1 expression. The viral protein Tax transcriptionally activated caveolin-1 gene through nuclear factor-κB and cAMP response element binding protein signal pathways. HTLV-1–infected T-cell lines, and ATL cells are known to be resistant to transforming growth factor β (TGF-β)–induced growth inhibition. Caveolin-1 was colocalized with TGF-β type I receptor in HTLV-1–infected T-cell lines and suppressed TGF-β signaling. Caveolin-1 knockdown in an HTLV-1–infected T-cell line exhibited susceptibility to TGF-β. Thus, we describe a new function for Tax, repression of TGF-β signaling through caveolin-1 expression, which may play a critical role in ATL leukemogenesis.

Adult T Cell Leukemia/Lymphoma (ATLL) Is a Malignant Counterpart of Regulatory T Cells (Treg).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 82-82
Author(s):  
Tomoko Kohno ◽  
Yasuaki Yamada ◽  
Norihiko Akamatsu ◽  
Shimeru Kamihira ◽  
Masao Tomonaga ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Lines ◽  
Acute Type ◽  
Cell Leukemia ◽  
Chronic Type ◽  
Adult T Cell Leukemia ◽  
Atll Cell ◽  
T Cell Lines

Abstract Adult T cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder caused by a retrovirus, human T-lymphotropic virus type 1 (HTLV-1). ATLL is subclassified into four subtypes, smoldering, chronic, acute, and lymphoma. The acute type progresses rapidly and is usually resistant to conventional chemotherapy. In contrast, the chronic type shows an indolent clinical course and the patients survive for several years, even without chemotherapy. Irrespective of the subtypes, however, ATLL patients are in a severely immune-suppressed condition and can easily acquire opportunistic infections such as Pneumocystis Carinii pneumonitis. Suppression of cell-mediated immunity has also been reported in HTLV-1 carriers. Although ATLL cells show the activated helper/inducer T-cell phenotypes, CD4+ and CD25+, they exhibit strong immune-suppressive activity in vitro. The recent notion of CD4+ CD25+ regulatory T cells (Treg) prompted us to investigate the origin of ATLL cells from the standpoint of Treg. Forkhead/winged helix transcription factor (Foxp3) is a functional marker of Treg, which plays a central role in their generation. There are other marker molecules for Treg, including glucocorticoid-induced TNFR family-related protein (GITR) and the chemokine receptors CCR4 and CCR8. In the present study, we examined primary ATLL cells from 48 patients: 36 patients with acute type and 12 patients with chronic type. We also examined ATLL cell lines, HTLV-1-infected T-cell lines and peripheral blood mononuclear cells (PBMC) from healthy adults as control cells. We used RT-PCR for detection of Foxp3, GITR, CCR4, and CCR8 mRNA expression. Foxp3 and/or GITR mRNA were detected in over 90% of the patients, and 50% of the patients expressed both. There was no difference between subtypes. In contrast, Foxp3 and GITR mRNA were scarcely detected in the PBMC from healthy adults. Furthermore, we confirmed GITR expression at the protein level by flow cytometry. CCR4 and CCR8 mRNA were also detected in almost all ATLL samples, at significantly higher levels than in the normal PBMC. Corresponding to the results of the primary cells, ATLL cell lines and HTLV-1-infected T-cell lines also expressed GITR mRNA, although HTLV-1-negative cell lines, Jurkat and Molt4, completely lack it. Next, we examined whether GITR affects ATLL cell proliferation using a GITR- expressing IL-2-dependent ATLL cell line, KK1. We found that GITR ligand induced proliferation of KK1 cells in an IL-2-negative condition. Thus, these results indicate the Treg origin of ATLL cells and show that GITR expression is possibly involved in the development of ATLL.

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