Morphologic and Immunohistochemical Characterization of Spontaneous Lymphoma/Leukemia in NSG Mice

The NOD.Cg- Prkdcscid Il2rgtm1Wjl/SzJ strain (NOD scid gamma, NSG) is a severely immunodeficient inbred laboratory mouse used for preclinical studies because it is amenable to engraftment with human cells. Combining scid and Il2rgnull mutations results in severe immunodeficiency by impairing the maturation, survival, and functionality of interleukin 2–dependent immune cells, including T, B, and natural killer lymphocytes. While NSG mice are reportedly resistant to developing spontaneous lymphomas/leukemias, there are reports of hematopoietic cancers developing. In this study, we characterized the immunophenotype of spontaneous lymphoma/leukemia in 12 NSG mice (20 to 38 weeks old). The mice had a combination of grossly enlarged thymus, spleen, or lymph nodes and variable histologic involvement of the bone marrow and other tissues. All 12 lymphomas were diffusely CD3, TDT, and CD4 positive, and 11 of 12 were also positive for CD8, which together was consistent with precursor T-cell lymphoblastic lymphoma/leukemia (pre-T-LBL). A subset of NSG tissues from all mice and neoplastic lymphocytes from 8 of 12 cases had strong immunoreactivity for retroviral p30 core protein, suggesting an association with a viral infection. These data highlight that NSG mice may develop T-cell lymphoma at low frequency, necessitating the recognition of this spontaneously arising disease when interpreting studies.

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Expression of A2B adenosine receptors in human lymphocytes: their role in T cell activation

Journal of Cell Science ◽

10.1242/jcs.112.4.491 ◽

1999 ◽

Vol 112 (4) ◽

pp. 491-502

Author(s):

M. Mirabet ◽

C. Herrera ◽

O.J. Cordero ◽

J. Mallol ◽

C. Lluis ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Human Peripheral Blood ◽

Human Lymphocytes ◽

Interleukin 2 ◽

Cell Receptor ◽

Physiological Characterization ◽

A2a Receptors

Extracellular adenosine has a key role in the development and function of the cells of the immune system. Many of the adenosine actions seem to be mediated by specific surface receptors positively coupled to adenylate cyclase: A2A and A2B. Despite the fact that A2A receptors (A2ARs) can be easily studied due to the availability of the specific agonist CGS21680, a pharmacological and physiological characterization of adenosine A2B receptors (A2BRs) in lymphocytes has not been possible due to the lack of suitable reagents. Here we report the generation and characterization of a polyclonal antipeptide antibody raised against the third extracellular loop of the A2BR human clone which is useful for immunocytochemical studies. This antibody has permitted the detection of A2BR+ cells in lymphocyte samples isolated from human peripheral blood. The pharmacology of cAMP-producing compounds is consistent with the presence of functional A2BRs but not of A2A receptors in these human cells. The percentage of A2BR-expressing cells was similar in the CD4(+) or CD8(+) T cell subpopulations. Interestingly activation signals delivered by either phytohemagglutinin or anti-T cell receptor/CD3 complex antibodies led to a significant increase in both the percentage of cells expressing the receptor and the intensity of the labeling. These receptors are functional since interleukin-2 production in these cells is reduced by NECA but not by R-PIA or CGS21680. These results show that A2BR expression is regulated in T cell activation and suggest that the role of adenosine in lymphocyte deactivation is mediated by A2BRs.

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Further Characterization of an Interleukin-2-1Ike Cytokine Produced byXenopus LaevisT Lymphocytes

Developmental Immunology ◽

10.1155/1993/68197 ◽

1993 ◽

Vol 3 (3) ◽

pp. 231-238 ◽

Cited By ~ 10

Author(s):

Laura Haynes ◽

Nicholas Cohen

Keyword(s):

T Cell ◽

South African ◽

Interleukin 2 ◽

Biological Properties ◽

Biologically Active ◽

Lectin Affinity Chromatography ◽

Sds Page ◽

Cell Mitogen ◽

Clawed Frog

A T-cell growth factor (TCGF) is produced by antigen- or mitogen-stimulated T lymphocytes from the South African clawed frogXenopus laevis. This study further defines the physical and biological properties of this cytokine and demonstrates that TCGF is biochemically similar to mammalian interleukin-2 (IL-2). Biologically active TCGF eluted from SDS-PAGE displays a Mrof 16 kD and lectin-affinity chromatography indicates that the three-dimensionmal configuration of carbohydrates on TCGF and human IL-2 is similar. Secretion of TCGF is detectable 1 day after stimulation of splenocytes with the T-cell mitogen phytohemagglutinin (PHA) and peaks following 2 to 3 days of stimulation. Finally, despite the biological and physical similarities betweenXenopusTCGF and mammalian IL-2, anti-human IL-2 monoclonal antibodies do not recognizeXenopusTCGF.

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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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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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