scholarly journals Highly Enhanced Expression of CD70 on Human T-Lymphotropic Virus Type 1-Carrying T-Cell Lines and Adult T-Cell Leukemia Cells

2008 ◽  
Vol 82 (8) ◽  
pp. 3843-3852 ◽  
Author(s):  
Masanori Baba ◽  
Mika Okamoto ◽  
Takayuki Hamasaki ◽  
Sawako Horai ◽  
Xin Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Cell Leukemia ◽  
Expression Levels ◽  
T Lymphotropic Virus ◽  
Adult T Cell Leukemia ◽  
Enhanced Expression ◽  
T Cell Lines

ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL). In Japan, the number of HTLV-1 carriers is estimated to be 1.2 million and more than 700 cases of ATL have been diagnosed every year. Considering the poor prognosis and lack of curative therapy of ATL, it seems mandatory to establish an effective strategy for the treatment of ATL. In this study, we attempted to identify the cell surface molecules that will become suitable targets of antibodies for anti-ATL therapy. The expression levels of approximately 40,000 host genes of three human T-cell lines carrying HTLV-1 genomes were analyzed by oligonucleotide microarray and compared with the expression levels of the genes in an HTLV-1-negative T-cell line. The HTLV-1-carrying T-cell lines used for experiments had totally different expression patterns of viral genome. Among the genes evaluated, the expression levels of 108 genes were found to be enhanced more than 10-fold in all of the T-cell lines examined and 11 of the 108 genes were considered to generate the proteins expressed on the cell surface. In particular, the CD70 gene was upregulated more than 1,000-fold and the enhanced expression of the CD70 molecule was confirmed by laser flow cytometry for various HTLV-1-carrying T-cell lines and primary CD4+ T cells isolated from acute-type ATL patients. Such expression was not observed for primary CD4+ T cells isolated from healthy donors. Since CD70 expression is strictly restricted in normal tissues, such as highly activated T and B cells, CD70 appears to be a potential target for effective antibody therapy against ATL.

scholarly journals Possible origin of adult T-cell leukemia/lymphoma cells from human T lymphotropic virus type-1-infected regulatory T cells

2005 ◽  
Vol 96 (8) ◽  
pp. 527-533 ◽  
Author(s):  
Tomoko Kohno ◽  
Yasuaki Yamada ◽  
Norihiko Akamatsu ◽  
Simeru Kamihira ◽  
Yoshitaka Imaizumi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Virus Type ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Lymphoma Cells ◽  
T Lymphotropic Virus ◽  
Adult T Cell Leukemia

Clinical significance of CD70 expression on T cells in human T-lymphotropic virus type-1 carriers and adult T cell leukemia/ lymphoma patients

2015 ◽  
Vol 57 (3) ◽  
pp. 685-691
Author(s):  
Izumi Masamoto ◽  
Makoto Yoshimitsu ◽  
Ayako Kuroki ◽  
Sawako Horai ◽  
Chibueze Chioma Ezinne ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Significance ◽  
Virus Type ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
T Lymphotropic Virus ◽  
Adult T Cell Leukemia

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.

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.

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

Abstract 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 Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia.

1990 ◽  
Vol 172 (1) ◽  
pp. 121-129 ◽  
Author(s):  
S J Kim ◽  
J H Kehrl ◽  
J Burton ◽  
C L Tendler ◽  
K T Jeang ◽  
...  
Keyword(s):  
T Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Leukemic Cells ◽  
Tgf Beta ◽  
Cell Leukemia ◽  
T Lymphotropic Virus ◽  
Adult T Cell Leukemia ◽  
Growth Factor Beta

We examined the effect of the human T lymphotropic virus type 1 (HTLV-I) Tax gene product on the human transforming growth factor beta 1 (TGF-beta 1) promoter. Transfection of deleted constructs of the TGF-beta 1 promoter revealed regions homologous with AP-1 binding sites that were required for Tax-induced transactivation of the TGF-beta 1 promoter. In addition, we examined the expression and secretion of TGF-beta in fresh leukemic cells isolated from patients with adult T cell leukemia (ATL) and in HTLV-1-infected T cell lines. We report that fresh leukemic cells from ATL patients constitutively produce high levels of TGF-beta 1 mRNA and secrete TGF-beta 1 but not TGF-beta 2 into the culture medium. In addition, long-term ATL cell lines expressed significant amounts of TGF-beta 1 mRNA as well as detectable levels of TGF-beta 1 protein. These results suggest a role for Tax in the upregulation of TGF-beta 1 in HTLV-I-infected cells.

Frequent expression of interleukin-9 mRNA and infrequent involvement of interleukin-9 in proliferation of primary adult T-cell leukemia cells and HTLV-I infected T-cell lines

1997 ◽  
Vol 21 (3) ◽  
pp. 211-216 ◽  
Author(s):  
Kakushi Matsushita ◽  
Naomichi Arima ◽  
Hideo Ohtsubo ◽  
Hiroshi Fujiwara ◽  
Shiroh Hidaka ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Leukemia Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
T Cell Lines ◽  
Interleukin 9

Case Report: HTLV-1–Induced Adult T-Cell Leukemia and Tropical Spastic Paresis

2021 ◽  
Author(s):  
Reece Rosenthal ◽  
Julika Kaplan ◽  
Mohammed Ahmed ◽  
Martha Mims ◽  
Jill E. Weatherhead
Keyword(s):  
T Cell ◽  
Lower Extremity ◽  
Spastic Paraparesis ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Lower Extremity Weakness ◽  
T Lymphotropic Virus ◽  
Adult T Cell Leukemia ◽  
Spastic Paresis

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus endemic in many areas around the world. HTLV-1 can induce the development of adult T-cell leukemia (ATL) or myelopathy/tropical spastic paraparesis (HAM/TSP). We report a patient who presented to our outpatient clinic with massive splenomegaly, weight loss, urinary retention, and lower extremity weakness for the previous 3 years. The patient was found to have positive HTLV-1 by ELISA and Western blot from peripheral blood. Evaluation of the spleen demonstrated T-cell large granular lymphocyte leukemia consistent with ATL. In addition to progressive lower extremity weakness, hyperreflexia and clonus, cerebral spinal fluid was positive for HTLV-1 by ELISA and had a reversed CD4-to-CD8 ratio consistent with HAM/TSP. These findings suggest HTLV-1 induced ATL and HAM/TSP presenting simultaneously in the same patient.

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