Receptor-mediated endocytosis of interleukin 2 in a human tumor T cell line. Degradation of interleukin 2 and evidence for the absence of recycling of interleukin receptors.

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).

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Loss of encephalitogenicity of a myelin basic protein-specific T cell line is associated with a phenotypic change but not with alteration in production of interleukin-2, γ-interferon or tumour necrosis factor

Journal of Neuroimmunology ◽

10.1016/0165-5728(90)90052-o ◽

1990 ◽

Vol 30 (1) ◽

pp. 53-59 ◽

Cited By ~ 8

Author(s):

Michael J. Day ◽

Don W. Mason

Keyword(s):

T Cell ◽

Myelin Basic Protein ◽

Cell Line ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Basic Protein ◽

Interleukin 2 ◽

Phenotypic Change ◽

Γ Interferon ◽

Necrosis Factor

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Selection and characterization of monoclonal antibodies to the idiotype-like structure of an interleukin-2-producing human leukemia t-cell line

International Journal of Cancer ◽

10.1002/ijc.2910360219 ◽

1985 ◽

Vol 36 (2) ◽

pp. 253-259 ◽

Cited By ~ 15

Author(s):

Alessandro Moretta ◽

Giuseppe Pantaleo ◽

Miguel Lopez-Botet ◽

Lorenzo Moretta

Keyword(s):

Monoclonal Antibodies ◽

T Cell ◽

Cell Line ◽

Interleukin 2 ◽

Human Leukemia

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The ζ Isoform of Protein Kinase C Controls Interleukin-2-Mediated Proliferation in a Murine T Cell Line: Evidence for an Additional Role of Protein Kinase C ϵ and β

Experimental Cell Research ◽

10.1006/excr.1995.1136 ◽

1995 ◽

Vol 218 (1) ◽

pp. 105-113 ◽

Cited By ~ 25

Author(s):

Javier Gómez ◽

Christina Pitton ◽

Alphonse Garcı́a ◽

Ana Martinez De Aragón ◽

Augusto Silva ◽

...

Keyword(s):

Protein Kinase C ◽

T Cell ◽

Protein Kinase ◽

Cell Line ◽

Interleukin 2 ◽

Kinase C ◽

Additional Role

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Biochemical and biological characterization of lymphocyte regulatory molecules. V. Identification of an interleukin 2-producing human leukemia T cell line.

Journal of Experimental Medicine ◽

10.1084/jem.152.6.1709 ◽

1980 ◽

Vol 152 (6) ◽

pp. 1709-1719 ◽

Cited By ~ 259

Author(s):

S Gillis ◽

J Watson

Keyword(s):

T Cell ◽

Cell Line ◽

Cell Lines ◽

Human Peripheral Blood ◽

Fatty Acid Derivative ◽

Interleukin 2 ◽

Leukemia Cell ◽

Tumor Cell Line ◽

Human Leukemia

To isolate a stable tumor cell line capable of producing human interleukin 2 (IL-2; formerly referred to as T cell growth factor), 16 human T and B leukemia cell lines were screened for constitutive and mitogen-stimulated IL-2 production. We found that the T cell leukemia line designated Jurkat-FHCRC produced > 200 U/ml of IL-2 activity after a 24-h stimulation with T cell mitogens. Peak mitogen-induced IL-2 activity was found in supernates harvested from 24-h Jurkat-FHCRC cell cultures stimulated with either 1% phytohemagglutinin or 20 microgram/ml concanavalin A. Addition of the fatty acid derivative phorbol myristate acetate to mitogen-stimulated cultures increased Jurkat-FHCRC IL-2 production to concentrations > 400 U/ml. IL-2 activity observed in such cases represented between 100--300 times that produced in conventional cultures of mitogen- or alloantigen-stimulated normal human peripheral blood or splenic lymphocytes. Jurkat-FHCRC-derived conditioned medium demonstrated equal capacity to promote the sustained in vitro proliferation of either murine or human activated T cell lines confirming the ability of Jurkat-FHCRC cells to produce human IL-2. These studies identify a new source of human IL-2 and establish a valuable reagent for the isolation and further molecular characterization of this immunoregulatory molecule.

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Idiotype-reactive T-cell subsets and tumor load in monoclonal gammopathies

Blood ◽

10.1182/blood.v86.8.3043.bloodjournal8683043 ◽

1995 ◽

Vol 86 (8) ◽

pp. 3043-3049 ◽

Cited By ~ 3

Author(s):

Q Yi ◽

A Osterborg ◽

S Bergenbrant ◽

H Mellstedt ◽

G Holm ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Interleukin 2 ◽

Human Tumor ◽

Stage I ◽

Stage Ii ◽

T Cell Subsets ◽

Ifn Gamma ◽

Tumor Load ◽

Th1 And Th2

The presence of idiotype-reactive T-cell subsets and their relation to the tumor load were analyzed in 9 patients with monoclonal gammopathy of undetermined significance (MGUS), in 12 patients with multiple myeloma (MM) clinical stage I, and in 9 patients with MM stage II/III. An enzyme-linked immunospot assay was used to identify interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, or IL-4-secreting T cells after stimulation by F(ab')2 fragments of monoclonal IgG. The response to autologous IgG was significantly higher than that induced by isotypic monoclonal IgG. Comparable results were obtained in a proliferation assay (3H-thymidine incorporation). A total of 8 of 9 patients with MGUS, 7 of 12 patients with MM stage I, and 3 of 9 with MM stage II/III had T cells secreting IFN-gamma and/or IL-2 (T helper [Th1] type-1 cells), whereas cells secreting both Th1 and Th2 or Th0 types of cytokines were more frequent in patients with MM, particularly in those with MM stage II/III. The number and frequency of Th1-type cells were significantly higher in MGUS patients as compared with those of MM stage II/III. The results indicate that idiotype-reactive T cells of the Th1 and Th2 or Th0 subsets were present in MGs and might provide indirect evidence that idiotype-reactive Th1-type cells may have a regulatory impact on the human tumor B cells.

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Establishment of a karyotypically normal cytotoxic leukemic T-cell line from a T-ALL sample engrafted in SCID mice

Blood ◽

10.1182/blood.v81.10.2714.bloodjournal81102714 ◽

1993 ◽

Vol 81 (10) ◽

pp. 2714-2722

Author(s):

A Cesano ◽

R O'Connor ◽

PC Nowell ◽

B Lange ◽

SC Clark ◽

...

Keyword(s):

T Cell ◽

Cell Line ◽

Chromosomal Abnormalities ◽

Lymphoblastic Leukemia ◽

Interleukin 2 ◽

Cell Subset ◽

Scid Mice ◽

Leukemic Cells ◽

Cytotoxic T Cell ◽

Tumoricidal Activity

Bone marrow (BM) cells from a child with an immature (CD3-) acute T lymphoblastic leukemia (T-ALL) bearing no chromosomal abnormalities failed to grow in long-term culture in the presence or absence of recombinant human (rh) growth factors but could be engrafted in severe combined immunodeficient (SCID) mice and induced leukemia. The leukemic cells recovered from the animal tissues could be adapted to grow in vitro in the presence of rh interleukin-2 (IL-2) and give rise to a growth factor-dependent cell line designated TALL-107. This cell line expresses T-cell-specific mature markers (CD2, CD3/T-cell receptor [TCR] alpha beta, CD8, CD56), and its growth can be inhibited by IL-4 of all the cytokines tested. Similar to the original leukemic blasts, TALL-107 cells are clonal, have rearranged TCR-beta, gamma, and delta loci, and a normal 46 XY karyotype. However, unlike the patient's BM cells, the TALL-107 cell line displays potent tumoricidal activity that is not major histocompatibility complex restricted. The magnitude of mRNA expression of perforin and serine esterases and of lytic activity depends on the doses of IL-2 added. TALL-107 cells can also be triggered by CD3- and CD2-specific monoclonal antibodies (MoAbs) to mediate reverse tumor cell lysis. In addition, this cell line produces high levels of interferon gamma and tumor necrosis factor alpha on stimulation with anti-CD3 and/or anti-CD2 MoAb both in the presence or absence of IL-2. The overall data indicate that the SCID mouse is able to support the functional maturation and expansion of a cytotoxic T- cell subset from some types of T-ALL.

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