scholarly journals Large granular lymphocytes from patients with expanded LGL populations acquire cytotoxic functions and release lymphokines upon in vitro activation

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1095-1100
Author(s):  
V Pistoia ◽  
EF Prasthofer ◽  
AB Tilden ◽  
JC Barton ◽  
M Ferrarini ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Cytolytic Activity ◽  
Target Cells ◽  
Large Granular Lymphocytes ◽  
Functional Capabilities ◽  
Hla Dr ◽  
Recombinant Interleukin 2 ◽  
Functional Features ◽  
Granular Lymphocytes

The phenotypic and functional features of purified large granular lymphocytes (LGL) from ten patients with LGL population expansions and cytopenias are described. The predominant LGL phenotypes were T3+, T8+, Leu-11+/-; however, in two patients, LGL expressed a T3-, Leu-11+ phenotype. Variable combinations of other LGL markers (OKM1, Leu-7), and HLA-DR were detected in individual cases. In nine of ten cases, freshly isolated LGL did not exert cytolytic activity for K562 target cells, but purified LGL cultured in the presence of recombinant interleukin 2 (rIL2) acquired potent cytotoxic activity in all cases tested. LGL did not proliferate in response to phytohemagglutinin (PHA). However, LGL released variable amounts of IL2 and gamma- interferon (gamma-IFN) after PHA stimulation. In some cases, stimulation of fresh LGL with recombinant IL2 induced production of gamma-IFN. No correlation was found between the functional capabilities and the original phenotype of the expanded LGL populations.

scholarly journals Large granular lymphocytes from patients with expanded LGL populations acquire cytotoxic functions and release lymphokines upon in vitro activation

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1095-1100 ◽  
Author(s):  
V Pistoia ◽  
EF Prasthofer ◽  
AB Tilden ◽  
JC Barton ◽  
M Ferrarini ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Cytolytic Activity ◽  
Target Cells ◽  
Large Granular Lymphocytes ◽  
Functional Capabilities ◽  
Hla Dr ◽  
Recombinant Interleukin 2 ◽  
Functional Features ◽  
Granular Lymphocytes

Abstract The phenotypic and functional features of purified large granular lymphocytes (LGL) from ten patients with LGL population expansions and cytopenias are described. The predominant LGL phenotypes were T3+, T8+, Leu-11+/-; however, in two patients, LGL expressed a T3-, Leu-11+ phenotype. Variable combinations of other LGL markers (OKM1, Leu-7), and HLA-DR were detected in individual cases. In nine of ten cases, freshly isolated LGL did not exert cytolytic activity for K562 target cells, but purified LGL cultured in the presence of recombinant interleukin 2 (rIL2) acquired potent cytotoxic activity in all cases tested. LGL did not proliferate in response to phytohemagglutinin (PHA). However, LGL released variable amounts of IL2 and gamma- interferon (gamma-IFN) after PHA stimulation. In some cases, stimulation of fresh LGL with recombinant IL2 induced production of gamma-IFN. No correlation was found between the functional capabilities and the original phenotype of the expanded LGL populations.

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.

scholarly journals Production of plasminogen activator by human natural killer cells. Large granular lymphocytes.

1984 ◽  
Vol 159 (3) ◽  
pp. 935-951 ◽  
Author(s):  
R H Goldfarb ◽  
T Timonen ◽  
R B Herberman
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Plasminogen Activator ◽  
Surface Membrane ◽  
Interleukin 2 ◽  
Cytolytic Activity ◽  
Large Granular Lymphocytes ◽  
A Cell ◽  
Chediak Higashi Syndrome ◽  
Granular Lymphocytes

In this report we have used highly purified populations of natural killer (NK) cells: large granular lymphocytes (LGL). This study demonstrates that freshly isolated and interleukin 2-cultured LGL produce the specific neutral serine protease, plasminogen activator (PA). We have found that the enzyme is expressed in both an extracellular form as well as in a cell-associated form. Upon subcellular distribution the latter form of the enzyme is associated with a cell-surface membrane-enriched fraction. LGL PA exists in multiple molecular weight forms ranging from 100,000 to 26,000. Interferon (IFN), the major positive regulator of NK cytolytic activity, caused a substantial enhancement of cell-associated, but not extracellular, PA. In contrast, LGL isolated from patients with Chediak-Higashi syndrome, who are known to be defective in NK activity, displayed low PA activity, altered morphology, and low NK killing relative to LGL isolated from normal donors. The possible role of LGL PA in the lysis of tumor cells by NK cells, either directly or indirectly, is discussed.

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.

Modulation of NK cell cytolytic activity by macrophages in chronically exercise-stressed mice

1997 ◽  
Vol 83 (3) ◽  
pp. 845-850 ◽  
Author(s):  
Sally E. Blank ◽  
T. Bucky Jones ◽  
Eric G. Lee ◽  
C. Jayne Brahler ◽  
Randle M. Gallucci ◽  
...  
Keyword(s):  
Nk Cell ◽  
Cell Activity ◽  
Cytolytic Activity ◽  
Moderate Intensity ◽  
Large Granular Lymphocytes ◽  
Nk Cell Activity ◽  
Murine Splenocytes ◽  
Vitro Assay ◽  
Granular Lymphocytes

Blank, Sally E., T. Bucky Jones, Eric G. Lee, C. Jayne Brahler, Randle M. Gallucci, Marne L. Fox, and Gary G. Meadows.Modulation of NK cell cytolytic activity by macrophages in chronically exercise-stressed mice. J. Appl. Physiol. 83(3): 845–850, 1997.—This study was designed to investigate the effects of moderate-intensity endurance training on basal natural killer (NK) cell cytolytic activity in murine splenocytes that were enriched for 1) NK1.1+ cells or 2) macrophages and NK1.1+ cells. Mice were assigned to sedentary (Sed), treadmill control (TM), or treadmill-trained (Trn) groups. Splenocyte number, the percentages of NK1.1+, large granular lymphocytes (NK1.1+, LGL-1+), and other subpopulations did not change in Trn mice. Approximately 70% of cells enriched for NK1.1+expressed this surface antigen. Lytic units (LU) expressed per LGL-1+ cell were significantly lower in Trn [83.9 ± 3.2 (SE)] compared with Sed (109.5 ± 7.5) and TM (101.3 ± 6.4) groups. When macrophages remained in the in vitro assay, LU per LGL-1+ cell did not differ across groups. The results indicate that highly enriched NK1.1+ cells from Trn mice had lower NK cell activity compared with Sed mice. No differences in NK cell activity were observed when cells were enriched for NK1.1+ cells and macrophages. These findings support the hypothesis that macrophage modulation of NK cells may be one mechanism contributing to augmented basal NK cell activity in endurance-trained individuals.

Sign in / Sign up

Export Citation Format

Share Document