Establishment of an interleukin 2-dependent human T cell line from a patient with T cell chronic lymphocytic leukemia who is not infected with human T cell leukemia/lymphoma virus

Hori, Tomohide; Uchiyama, Takashi; Tsudo, Mitsuru; Umadome, H; Ohno, Hitoshi; Fukuhara, Shirou; Kita, K; Uchino, Haruto

doi:10.1182/blood.v70.4.1069.1069

Cited by 155 publications

(50 citation statements)

References 22 publications

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“…The ␥ c family members IL-2, IL-7, and IL-15 share the ability to induce proliferation of T lymphocytes; therefore, we aimed to determine whether IL-7 and/or IL-15 could replace IL-2 and promote proliferation of Kit225 T cells [29]. For that purpose, Kit225 cells were synchronized at G1 phase of the cell cycle by depriving with IL-2 for 48 h followed by reintroduction of each cytokine alone at the indicated concentration every 48 h. As expected, nonproliferating starved cells reentered the cell cycle and started growing in the presence of IL-2 ( Fig.…”

Section: Il-15 But Not Il-7 Can Mimic the Proliferative Effect Of Imentioning

confidence: 99%

Simultaneous dissection and comparison of IL‐2 and IL‐15 signaling pathways by global quantitative phosphoproteomics

et al. 2014

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Common γ-chain family of cytokines (IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, where IL stands for interleukin) are key regulators of the immune homeostasis that exhibit pleiotropic biological activities and even sometimes redundant roles as a result of the utilization of the same receptor subunit. However, they also exert distinct functions that make each of them to be indispensable. For instance, all family members can act as T-cell growth factors; however, we found that IL-15 but not IL-7 can replace IL-2 to promote and sustain the proliferation of Kit225T cells. In addition to the γ-chain, IL-2 and IL-15 share the β-chain, which creates the paradox of how they can trigger diverse phenotypes despite signaling through the same receptors. To investigate this paradigm, we combined SILAC with enrichment of tyrosine-phosphorylated proteins and peptides followed by mass spectrometric analysis to quantitatively assess the signaling networks triggered downstream IL-2/IL-2R and IL-15/IL-15R. This study confirmed that the transduction pathways initiated by both cytokines are highly similar and revealed that the main signaling branches, JAK/STAT, RAS/MAPK and PI3K/AKT, were nearly equivalently activated in response to both ILs. Despite that, our study revealed that receptor internalization rates differ in IL-2- and IL-15-treated cells indicating a discrete modulation of cytokine signaling. All MS data have been deposited in the ProteomeXchange with identifier PXD001129 (http://proteomecentral.proteomexchange.org/dataset/PXD001129).

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Section: Il-15 But Not Il-7 Can Mimic the Proliferative Effect Of Imentioning

confidence: 99%

Simultaneous dissection and comparison of IL‐2 and IL‐15 signaling pathways by global quantitative phosphoproteomics

et al. 2014

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“…The human T-cell line, Kit-225, a generous gift of Dr Paul Brennan (London, UK), constitutively expresses the high-affinity IL-2R (a, b and g chains) (12). The cell line was originally derived from a human adult T-cell leukemia (13) and was maintained in 10K medium (RPMI 1640 medium supplemented with 10% fetal calf serum, 1% L-glutamine, 1% penicillin/streptomycin), and 20 IU/mL of recombinant human IL-2 (rIL-2) (gift of Dr J. Spinwall, Roche Inc., Nutley, NJ). To maintain growth, the cells were split by 1:5 dilution in fresh media every third day.…”

Section: Cell Culture Stimulation and Proliferationmentioning

confidence: 99%

Effect of Anti‐IL‐2Rα Antibody on IL‐2‐induced Jak/STAT Signaling

Tkaczuk

Baksh

et al. 2002

American Journal of Transplantation

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Acute allograft rejection is driven by production of cytokines such as interleukin-2 (IL-2) that activate and expand alloreactive T cells by ligating high-affinity IL-2 receptors composed of three subunit chains: a, b, g. The a chain, expressed only on activated T cells, has become an important therapeutic target. Monoclonal antibodies (mAbs) that bind IL-2Ra chains significantly decrease transplant rejection. We examined the ability of the humanized anti-IL-2Ra antibody daclizumab to block highaffinity IL-2Rs and interrupt T-lymphocyte signaling. Our evaluation focused on a pathway critical for T-cell proliferation, the Jak/STAT pathway. Daclizumab markedly inhibited phosphorylation of the Jak1, Jak3 and STAT5a/b components of the IL-2R-dependent pathway. Suppression by daclizumab was associated with internalization of IL-2Ra but not IL-2Rbg chains. High IL-2 doses overcame daclizumab-induced blockade of Jak/ STAT phosphorylation despite absent cell surface highaffinity IL-2Rs. Under these circumstances, IL-2-mediated Jak/STAT pathway activation might be generated through residual intermediate affinity IL-2Rbg receptors, and this was demonstrated by complete blockade of signaling when anti-IL-2Rb monoclonal antibody was added. Humanized antibodies are an important part of strategies to induce alloantigen tolerance. Understanding the molecular events associated with their beneficial clinical effect is critical to design of future immunosuppressive strategies.

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“…The mechanism of IL-2 stimulation of the progression phase of the human T-cell response to mitogen is not completely understood, in part because of the difficulty in studying IL-2R expression and IL-2 production separately. Kit225 is a human IL-2-dependent T-cell line originally derived from peripheral mononuclear cells of a patient with chronic T-cell leukemia (Hori et al, 1987). These cells express an extremely high number of IL-2Ra and IL-2Rp receptors but do not produce IL-2.…”

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confidence: 99%

Signal transduction by interleukin 2 in human T cells: Activation of tyrosine and ribosomal S6 kinases and cell‐cycle regulatory genes

Sawami¹,

Terada²,

Franklin³

et al. 1992

Journal Cellular Physiology

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The early events of signal transduction associated with interleukin-2 (IL-2) binding to its receptor were examined using a human IL-2 dependent T-cell line, Kit225. Cell cycle analysis showed that 90% of Kit225 cells were in the G0/G1 phase after a 72-hr incubation in the absence of exogenous IL-2. At this point, stimulation of the cells with IL-2 resulted in the rapid initiation of RNA and DNA synthesis by 9 and 20 hr, respectively. Within 5 min after addition of IL-2, rapid activation of tyrosine and ribosomal S6 kinases was detected. Addition of IL-2 also increased mRNA levels for c-fos, c-myc, IL-2 receptor alpha, and IL-2 receptor beta chain. These events increased in the absence of detectable changes in free cytosolic [Ca2+]i, inositol phosphate metabolism, or the activity of several kinases including cAMP-dependent protein kinase, Ca2+/calmodulin-dependent protein kinase, or protein kinase C. These findings demonstrate that the signals triggered by IL-2 binding to its receptors are quickly transduced into the nucleus with increased mRNA transcription of activation-associated genes. Furthermore, the data indicate that tyrosine and ribosomal S6 kinases may be important for IL-2-induced cell growth.

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Establishment of an interleukin 2-dependent human T cell line from a patient with T cell chronic lymphocytic leukemia who is not infected with human T cell leukemia/lymphoma virus

Cited by 155 publications

References 22 publications

Simultaneous dissection and comparison of IL‐2 and IL‐15 signaling pathways by global quantitative phosphoproteomics

Simultaneous dissection and comparison of IL‐2 and IL‐15 signaling pathways by global quantitative phosphoproteomics

Effect of Anti‐IL‐2Rα Antibody on IL‐2‐induced Jak/STAT Signaling

Signal transduction by interleukin 2 in human T cells: Activation of tyrosine and ribosomal S6 kinases and cell‐cycle regulatory genes

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