Suppression of Human Immunoglobulin Synthesis by Interleukin-4 in Tandem with Interleukin-2 through Large Granular Lymphocytes

Pathobiology ◽  
1991 ◽  
Vol 59 (6) ◽  
pp. 391-395 ◽  
Author(s):  
Diane Bosse ◽  
Edwin Ades
Keyword(s):  
Interleukin 2 ◽  
Human Immunoglobulin ◽  
Interleukin 4 ◽  
Large Granular Lymphocytes ◽  
Immunoglobulin Synthesis ◽  
Granular Lymphocytes

scholarly journals Activation signals leading to proliferation of normal and leukemic CD3+ large granular lymphocytes

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1282-1285 ◽  
Author(s):  
JA Aprile ◽  
M Russo ◽  
MS Pepe ◽  
TP Jr Loughran
Keyword(s):  
Cell Cycle ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
Large Granular Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Incorporation Assay ◽  
Granular Lymphocytes

Abstract The activation signals leading to proliferation of normal and leukemic CD3+ large granular lymphocytes (LGL) were studied in vitro. Anti-CD3 monoclonal antibody (MoAb) alone (P less than .01) and recombinant interleukin-2 (IL-2) alone (P less than .01) caused significant stimulation of peripheral blood mononuclear cells (PBMC) from four CD3+ LGL leukemia patients, as measured in a 3H-thymidine incorporation assay. Recombinant interleukin-4 (IL-4) alone had no effect (P = .11). The combination signals of anti-CD3 MoAb and either IL-2 or IL-4 produced a proliferative response greater than anti-CD3 MoAb alone (P less than .01) or lymphokine alone (P less than .01). Leukemic LGL, purified by two-color sorting, were subsequently activated by anti-CD3 MoAb and IL-2 and assessed for DNA content by viable Hoechst No. 33342 (HO) staining. Results of these studies demonstrated that leukemic LGL were stimulated directly by anti-CD3 MoAb and IL-2, with the percentage of cells in cell cycle (S + G2/M) ranging from 16% to 72%. Normal CD3+ LGL were also stimulated to enter the cell cycle by anti-CD3 and IL-2. These results show that leukemic LGL proliferate in vitro after activation through the T-cell receptor and/or lymphokine.

scholarly journals Activation signals leading to proliferation of normal and leukemic CD3+ large granular lymphocytes

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1282-1285
Author(s):  
JA Aprile ◽  
M Russo ◽  
MS Pepe ◽  
TP Jr Loughran
Keyword(s):  
Cell Cycle ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
Large Granular Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Incorporation Assay ◽  
Granular Lymphocytes

The activation signals leading to proliferation of normal and leukemic CD3+ large granular lymphocytes (LGL) were studied in vitro. Anti-CD3 monoclonal antibody (MoAb) alone (P less than .01) and recombinant interleukin-2 (IL-2) alone (P less than .01) caused significant stimulation of peripheral blood mononuclear cells (PBMC) from four CD3+ LGL leukemia patients, as measured in a 3H-thymidine incorporation assay. Recombinant interleukin-4 (IL-4) alone had no effect (P = .11). The combination signals of anti-CD3 MoAb and either IL-2 or IL-4 produced a proliferative response greater than anti-CD3 MoAb alone (P less than .01) or lymphokine alone (P less than .01). Leukemic LGL, purified by two-color sorting, were subsequently activated by anti-CD3 MoAb and IL-2 and assessed for DNA content by viable Hoechst No. 33342 (HO) staining. Results of these studies demonstrated that leukemic LGL were stimulated directly by anti-CD3 MoAb and IL-2, with the percentage of cells in cell cycle (S + G2/M) ranging from 16% to 72%. Normal CD3+ LGL were also stimulated to enter the cell cycle by anti-CD3 and IL-2. These results show that leukemic LGL proliferate in vitro after activation through the T-cell receptor and/or lymphokine.

Electron microscopic observations on the accumulation of large granular lymphocytes (pit cells) and kupffer cells in the liver of rats treated with continuous infusion of interleukin-2

Hepatology ◽  
1990 ◽  
Vol 12 (6) ◽  
pp. 1365-1370 ◽  
Author(s):  
Luc Bouwens ◽  
Andreas Marinelli ◽  
Peter J. K. Kuppen ◽  
Alex M. M. Eggermont ◽  
Cornelis J. H. van de Velde ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Kupffer Cells ◽  
Interleukin 2 ◽  
Large Granular Lymphocytes ◽  
Electron Microscopic ◽  
Pit Cells ◽  
Granular Lymphocytes

scholarly journals Malignant clonal expansion of large granular lymphocytes with a Leu- 11+, Leu-7- surface phenotype: in vitro responsiveness of malignant cells to recombinant human interleukin 2

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1065-1073 ◽  
Author(s):  
S Koizumi ◽  
H Seki ◽  
T Tachinami ◽  
M Taniguchi ◽  
A Matsuda ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Receptor Expression ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Target Cells ◽  
Transferase Activity ◽  
Large Granular Lymphocytes ◽  
Surface Phenotype ◽  
Granular Lymphocytes ◽  
Leu 7

Abstract A 14-year-old Japanese female with neutropenia showed malignant proliferation of the large granular lymphocytes (LGLs). These LGLs were E rosette+ and Fc(IgG) receptor+ and therefore are referred to as T gamma lymphocytes. They were also Leu-11+ and OKT11+; however, they were clearly negative for Leu-7, OKT3, OKT8, OKM1, and HNK-1 antigens as well as for terminal deoxynucleotidyl transferase activity. Karyotype analysis revealed 47, XXX. The LGLs showed no rearrangement of T cell receptor C beta genes. The natural killer (NK) cell activity against K562 target cells was low, but was significantly augmented after stimulation by recombinant human interleukin 2 (IL 2) in contrast to minimal NK boosting by recombinant human gamma-interferon (gamma- IFN). Such a unique responsive ability to lymphokines was quite similar to that noted in fetal and cord blood cells. These LGLs also demonstrated a considerable increase in antibody-dependent cell- mediated cytotoxicity (ADCC) and lymphokine-activated killer (LAK) activity after a short incubation with IL 2. Although in a resting stage they showed no IL 2 receptor expression as examined by anti-Tac antibody, Tac antigen appeared after IL 2 treatment followed by a marked increase in 3H-thymidine incorporation and a remarkable production of gamma-IFN. To investigate the mechanism of neutropenia, in vitro IL 2-stimulated coculture studies of these cells with normal bone marrow cells were performed. Colony formation of myeloid progenitors (CFU-C) was significantly suppressed. In addition, the conditioned medium from IL 2-stimulated LGLs indicated a remarkable suppression of CFU-C. These results suggest that these LGLs with a Leu- 11+, Leu-7- surface phenotype might belong to a unique subset of pre-NK cells that are functionally and phenotypically similar to those represented at any early stage of human ontogeny and that they strongly express Tac antigen under the influence of IL 2 administration, followed by remarkable cell proliferation and gamma-IFN production.

Malignant clonal expansion of large granular lymphocytes with a Leu- 11+, Leu-7- surface phenotype: in vitro responsiveness of malignant cells to recombinant human interleukin 2

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1065-1073 ◽  
Author(s):  
S Koizumi ◽  
H Seki ◽  
T Tachinami ◽  
M Taniguchi ◽  
A Matsuda ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Receptor Expression ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Target Cells ◽  
Transferase Activity ◽  
Large Granular Lymphocytes ◽  
Surface Phenotype ◽  
Granular Lymphocytes ◽  
Leu 7

A 14-year-old Japanese female with neutropenia showed malignant proliferation of the large granular lymphocytes (LGLs). These LGLs were E rosette+ and Fc(IgG) receptor+ and therefore are referred to as T gamma lymphocytes. They were also Leu-11+ and OKT11+; however, they were clearly negative for Leu-7, OKT3, OKT8, OKM1, and HNK-1 antigens as well as for terminal deoxynucleotidyl transferase activity. Karyotype analysis revealed 47, XXX. The LGLs showed no rearrangement of T cell receptor C beta genes. The natural killer (NK) cell activity against K562 target cells was low, but was significantly augmented after stimulation by recombinant human interleukin 2 (IL 2) in contrast to minimal NK boosting by recombinant human gamma-interferon (gamma- IFN). Such a unique responsive ability to lymphokines was quite similar to that noted in fetal and cord blood cells. These LGLs also demonstrated a considerable increase in antibody-dependent cell- mediated cytotoxicity (ADCC) and lymphokine-activated killer (LAK) activity after a short incubation with IL 2. Although in a resting stage they showed no IL 2 receptor expression as examined by anti-Tac antibody, Tac antigen appeared after IL 2 treatment followed by a marked increase in 3H-thymidine incorporation and a remarkable production of gamma-IFN. To investigate the mechanism of neutropenia, in vitro IL 2-stimulated coculture studies of these cells with normal bone marrow cells were performed. Colony formation of myeloid progenitors (CFU-C) was significantly suppressed. In addition, the conditioned medium from IL 2-stimulated LGLs indicated a remarkable suppression of CFU-C. These results suggest that these LGLs with a Leu- 11+, Leu-7- surface phenotype might belong to a unique subset of pre-NK cells that are functionally and phenotypically similar to those represented at any early stage of human ontogeny and that they strongly express Tac antigen under the influence of IL 2 administration, followed by remarkable cell proliferation and gamma-IFN production.

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