Establishment of a cyclic adenosine monophosphate-dependent growing human T-cell line derived from an interleukin-2-dependent cell line

1990 ◽  
Vol 145 (2) ◽  
pp. 238-243 ◽  
Author(s):  
Toshikazu Takeshita ◽  
Kazuyuki Ohbo ◽  
Masataka Nakamura ◽  
Yuso Goto ◽  
Kazuo Sugamura
Author(s):  
Shota Uesugi ◽  
Mayuka Hakozaki ◽  
Yuko Kanno ◽  
Honoka Takahashi ◽  
Yui Kudo ◽  
...  

Abstract Ca2+ signaling is related to various diseases such as allergies, diabetes, and cancer. We explored Ca2+ signaling inhibitors in natural resources using a yeast-based screening method, and found bakkenolide B from the flower buds of edible wild plant, Petasites japonicus, using the YNS17 strain (zds1Δ erg3Δ pdr1/3Δ). Bakkenolide B exhibited growth-restoring activity against the YNS17 strain and induced Li+ sensitivity of wild-type yeast cells, suggesting that it inhibits the calcineurin pathway. Additionally, bakkenolide B inhibited interleukin-2 production at gene and protein levels in Jurkat cells, a human T cell line, but not the in vitro phosphatase activity of human recombinant calcineurin, an upstream regulator of interleukin-2 production. Furthermore, bakkenolide A showed weak activity in YNS17 and Jurkat cells compared with bakkenolide B. These findings revealed new biological effects and the structure-activity relationships of bakkenolides contained in Petasites japonicus as inhibitors of interleukin-2 production in human T cells.


Biochemistry ◽  
1989 ◽  
Vol 28 (4) ◽  
pp. 1791-1797 ◽  
Author(s):  
Rene Nordmann ◽  
Elsebeth Andersen ◽  
Rene Trussardi ◽  
Norman A. Mazer

AIDS ◽  
2000 ◽  
Vol 14 (12) ◽  
pp. 1701-1707 ◽  
Author(s):  
Stephen D. Schibeci ◽  
Alison O. Clegg ◽  
Robyn A. Biti ◽  
Kimitaka Sagawa ◽  
Graeme J. Stewart ◽  
...  

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 588-592 ◽  
Author(s):  
A Dautry-Varsat ◽  
A Hemar ◽  
V Cornet ◽  
V Duprez

Abstract The effect of cyclosporin A (CsA), a potent immunosuppressive agent, on a human T-cell line, IARC 301, which constitutively secretes interleukin-2 (IL-2) and expresses high-affinity IL-2 receptors, was investigated. We show that CsA inhibits IARC 301 cell growth. CsA also prevents the constitutive secretion of IL-2 in this T-cell line by blocking transcription of the IL-2 gene. If exogenous IL-2 is added together with CsA for 3 days, the cells grow as well as untreated controls. Thus, under such conditions, CsA inhibits IARC 301 growth by preventing its endogenous constitutive IL-2 synthesis. This demonstrates that IL-2 stimulates the proliferation of this cell line by an autocrine pathway, in agreement with our previous data. We also show for the first time, that CsA not only can inhibit IL-2 production of T cells upon activation, but that it can also prevent ongoing constitutive IL-2 synthesis of a T-cell line. Autocrine growth stimulation of tumor cells by cytokines has been demonstrated in a few cases. CsA inhibits synthesis of several cytokines. Probing for the autocrine growth of tumor cells by studying the effect of CsA and its reversibility by cytokines on their proliferation may be simple and useful.


Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1069-1072 ◽  
Author(s):  
T Hori ◽  
T Uchiyama ◽  
M Tsudo ◽  
H Umadome ◽  
H Ohno ◽  
...  

We established an interleukin 2 (IL-2)-dependent human T cell line, Kit 225, from a patient with T cell chronic lymphocytic leukemia (T-CLL) with OKT3+, -T4+, -T8- phenotype. Southern blot analysis showed that Kit 225 is not infected with human T cell leukemia/lymphoma virus (HTLV) type I or II, and is probably derived from the major clone in the fresh leukemic cells. Kit 225 cells express a large amount of IL 2 receptors constitutively and their growth is absolutely dependent on IL 2. No other stimuli, such as lectins or antigens, are required for maintaining the responsiveness to IL 2. As abnormal IL 2 receptor expression was also seen originally in the fresh leukemic cells, the establishment of this cell line with IL 2 suggests that IL 2-mediated T cell proliferation is involved in the leukemogenesis of some cases of HTLV-negative T-CLL.


1996 ◽  
Vol 26 (6) ◽  
pp. 1322-1327 ◽  
Author(s):  
Masaya Higuchi ◽  
Hironobu Asao ◽  
Nobuyuki Tanaka ◽  
Katsuhiko Oda ◽  
Toshikazu Takeshita ◽  
...  

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 588-592
Author(s):  
A Dautry-Varsat ◽  
A Hemar ◽  
V Cornet ◽  
V Duprez

The effect of cyclosporin A (CsA), a potent immunosuppressive agent, on a human T-cell line, IARC 301, which constitutively secretes interleukin-2 (IL-2) and expresses high-affinity IL-2 receptors, was investigated. We show that CsA inhibits IARC 301 cell growth. CsA also prevents the constitutive secretion of IL-2 in this T-cell line by blocking transcription of the IL-2 gene. If exogenous IL-2 is added together with CsA for 3 days, the cells grow as well as untreated controls. Thus, under such conditions, CsA inhibits IARC 301 growth by preventing its endogenous constitutive IL-2 synthesis. This demonstrates that IL-2 stimulates the proliferation of this cell line by an autocrine pathway, in agreement with our previous data. We also show for the first time, that CsA not only can inhibit IL-2 production of T cells upon activation, but that it can also prevent ongoing constitutive IL-2 synthesis of a T-cell line. Autocrine growth stimulation of tumor cells by cytokines has been demonstrated in a few cases. CsA inhibits synthesis of several cytokines. Probing for the autocrine growth of tumor cells by studying the effect of CsA and its reversibility by cytokines on their proliferation may be simple and useful.


Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1069-1072 ◽  
Author(s):  
T Hori ◽  
T Uchiyama ◽  
M Tsudo ◽  
H Umadome ◽  
H Ohno ◽  
...  

Abstract We established an interleukin 2 (IL-2)-dependent human T cell line, Kit 225, from a patient with T cell chronic lymphocytic leukemia (T-CLL) with OKT3+, -T4+, -T8- phenotype. Southern blot analysis showed that Kit 225 is not infected with human T cell leukemia/lymphoma virus (HTLV) type I or II, and is probably derived from the major clone in the fresh leukemic cells. Kit 225 cells express a large amount of IL 2 receptors constitutively and their growth is absolutely dependent on IL 2. No other stimuli, such as lectins or antigens, are required for maintaining the responsiveness to IL 2. As abnormal IL 2 receptor expression was also seen originally in the fresh leukemic cells, the establishment of this cell line with IL 2 suggests that IL 2-mediated T cell proliferation is involved in the leukemogenesis of some cases of HTLV-negative T-CLL.


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