scholarly journals Characterization of natural killer cells with antileukemia activity following allogeneic bone marrow transplantation

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 722-728 ◽  
Author(s):  
T Hercend ◽  
T Takvorian ◽  
A Nowill ◽  
R Tantravahi ◽  
P Moingeon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Phenotypic Characterization ◽  
Allogeneic Bone

To identify cells with potential antileukemia activity following bone marrow transplantation, we have monitored immunologic reconstitution in a patient with acute lymphocytic leukemia in second remission who received intensive chemotherapy and total body irradiation followed by infusion of allogeneic histocompatible marrow. Prior to transplantation, donor bone marrow cells were depleted of T lymphocytes by in vitro treatment with anti-T12 monoclonal antibody and rabbit complement. In the first 3 weeks following bone marrow transplantation, the predominant regenerating mononuclear cell population in peripheral blood exhibited a phenotype characteristic of natural killer (NK) cells. After 4 weeks, T lymphocytes became predominant, but NK cells persisted. Cultured peripheral blood lymphocytes obtained 12 weeks posttransplant were able to display significant cytotoxicity against leukemic blasts that had been cryopreserved at the time of relapse 5 months prior to bone marrow transplantation. To further characterize those cells with antileukemia activity, we used in vitro cloning techniques to identify four monoclonal populations, termed TC12, -48, - 50, and -59, with strong antitumor activity. Cytogenetic analysis demonstrated that each clone was of donor origin. Phenotypic characterization showed that the four clones expressed NKH1A but did not express T3, T4, or T8 antigens. Three of the four clones expressed T11/E rosette antigen. Each clone exhibited strong cytotoxicity against genetically unrelated hematopoietic tumor cell lines such as K562, Molt- 4, JM, and U937. In addition, we found that these patient clones were similar to cloned NK cells previously derived from normal individuals. Taken together, these results suggest that at least some clones with antileukemia activity following bone marrow transplantation are cells with NK-like function and phenotype. Functional analysis of these cytolytic cells in larger numbers of patients will be necessary to determine the clinical significance of this finding.

scholarly journals Characterization of natural killer cells with antileukemia activity following allogeneic bone marrow transplantation

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 722-728 ◽  
Author(s):  
T Hercend ◽  
T Takvorian ◽  
A Nowill ◽  
R Tantravahi ◽  
P Moingeon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Phenotypic Characterization ◽  
Allogeneic Bone

Abstract To identify cells with potential antileukemia activity following bone marrow transplantation, we have monitored immunologic reconstitution in a patient with acute lymphocytic leukemia in second remission who received intensive chemotherapy and total body irradiation followed by infusion of allogeneic histocompatible marrow. Prior to transplantation, donor bone marrow cells were depleted of T lymphocytes by in vitro treatment with anti-T12 monoclonal antibody and rabbit complement. In the first 3 weeks following bone marrow transplantation, the predominant regenerating mononuclear cell population in peripheral blood exhibited a phenotype characteristic of natural killer (NK) cells. After 4 weeks, T lymphocytes became predominant, but NK cells persisted. Cultured peripheral blood lymphocytes obtained 12 weeks posttransplant were able to display significant cytotoxicity against leukemic blasts that had been cryopreserved at the time of relapse 5 months prior to bone marrow transplantation. To further characterize those cells with antileukemia activity, we used in vitro cloning techniques to identify four monoclonal populations, termed TC12, -48, - 50, and -59, with strong antitumor activity. Cytogenetic analysis demonstrated that each clone was of donor origin. Phenotypic characterization showed that the four clones expressed NKH1A but did not express T3, T4, or T8 antigens. Three of the four clones expressed T11/E rosette antigen. Each clone exhibited strong cytotoxicity against genetically unrelated hematopoietic tumor cell lines such as K562, Molt- 4, JM, and U937. In addition, we found that these patient clones were similar to cloned NK cells previously derived from normal individuals. Taken together, these results suggest that at least some clones with antileukemia activity following bone marrow transplantation are cells with NK-like function and phenotype. Functional analysis of these cytolytic cells in larger numbers of patients will be necessary to determine the clinical significance of this finding.

scholarly journals Effect of natural killer cells on syngeneic bone marrow: in vitro and in vivo studies demonstrating graft failure due to NK cells in an identical twin treated by bone marrow transplantation

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1043-1046
Author(s):  
GD Goss ◽  
MA Wittwer ◽  
WR Bezwoda ◽  
J Herman ◽  
A Rabson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Marrow Transplantation ◽  
Bone Marrow Failure ◽  
Cell Activity ◽  
High Dose

Bone marrow transplantation for severe idiopathic aplastic anemia was undertaken in a patient, using his monozygotic twin brother as the donor. In spite of the use of syngeneic bone marrow, failure of engraftment occurred on two occasions. In vitro studies demonstrated that natural killer (NK) cells from the recipient markedly inhibited the growth of donor bone marrow granulocyte progenitor cells. On a third attempt, successful bone marrow engraftment was achieved following high-dose cyclophosphamide, which has previously been shown to be inhibitory to NK cells. We conclude that NK cell activity may play an important role in bone marrow failure as well as being responsible for at least some cases of aplastic anemia.

scholarly journals CD16- CD56+ natural killer cells after bone marrow transplantation

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3239-3244 ◽  
Author(s):  
R Jacobs ◽  
M Stoll ◽  
G Stratmann ◽  
R Leo ◽  
H Link ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune System ◽  
Bone Marrow Transplantation ◽  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Nk Cell ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes

Abstract Natural killer (NK) cells are phenotypically defined as lymphocytes expressing the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3- CD16- CD56+ NK cell subset has been described in normal individuals representing less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for their reconstitution of the immune system during follow-up after autologous or allogeneic bone marrow transplantation. In 35% of these patients, two different NK cell subsets, namely CD56+dim and CD56+bright cells, were observed. The mean duration of these two subsets after transplant was 4 months. Sixty-five percent of the patients exhibited an increased number of NK cells, but only the typical CD16+ CD56+dim population. The CD56+bright subpopulation represented a particular CD3- CD16- NK subset, with posttransplant frequencies up to 70% of all NK cells and 40% of peripheral blood lymphocytes, respectively. In contrast to normal CD56+dim NK cells, CD56+bright cells coexpressed the activation antigens p75 beta-chain of interleukin-2 receptor (IL-2R), CD2R, and CD26, but were negative for CD16. NK and antibody-dependent cellular cytotoxicity activity of CD56+bright cells was low compared with CD56+dim NK cells. But using IL-2 and interferon gamma, their cytotoxicity could be enhanced even more than in CD56+dim lymphocytes. These different subsets may reflect distinct activation or differentiation steps of NK cells during reconstitution of the immune system. Their differential response to IL-2 may be of functional importance for posttransplant cytokine therapy.

scholarly journals In vitro evidence for disappearance of erythroid progenitor T suppressor cells following allogeneic bone marrow transplantation for severe aplastic anemia

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 144-150 ◽  
Author(s):  
KF Mangan ◽  
MT Mullaney ◽  
CS Rosenfeld ◽  
RK Shadduck
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
T Lymphocytes ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Before And After

Abstract In vitro coculture studies were performed in five patients with severe aplastic anemia (SAA) and their normal HLA-matched donors before and after allogeneic bone marrow transplantation (BMT) to determine whether the erythropoietic function of T cells is abnormal in this disorder. These coculture studies used fresh or cryopreserved marrow T lymphocytes with fresh or cryopreserved marrow T cell-depleted target cells. Four of five aplastic patients had little or no transfusion exposure before studies. The composite results showed that, in comparison to the erythropoietic effects of normal HLA-identical marrow T lymphocytes or engrafted T lymphocytes, T lymphocytes collected from the aplastic patients before BMT consistently suppressed or failed to support CFUE and BFUE growth optimally from autologous marrow, HLA- identical marrow, or engrafted aplastic T cell-depleted marrows. This T cell abnormality was not observed in four multiply transfused leukemics and three patients with myelodysplastic syndrome. Marker analyses of SAA marrow T lymphocytes performed before and after BMT suggested that the erythropoietic functional abnormality was due to abnormal marrow T cell composition reflecting an excess of activated Tac+, T3+, T11+ lymphocytes. Collectively, these in vitro studies provide firmer in vitro evidence implicating T cells in the pathogenesis of SAA. The erythropoietic T cells abnormalities in SAA are fully corrected by allogeneic BMT.

scholarly journals Effect of natural killer cells on syngeneic bone marrow: in vitro and in vivo studies demonstrating graft failure due to NK cells in an identical twin treated by bone marrow transplantation

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1043-1046 ◽  
Author(s):  
GD Goss ◽  
MA Wittwer ◽  
WR Bezwoda ◽  
J Herman ◽  
A Rabson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Marrow Transplantation ◽  
Bone Marrow Failure ◽  
Cell Activity ◽  
High Dose

Abstract Bone marrow transplantation for severe idiopathic aplastic anemia was undertaken in a patient, using his monozygotic twin brother as the donor. In spite of the use of syngeneic bone marrow, failure of engraftment occurred on two occasions. In vitro studies demonstrated that natural killer (NK) cells from the recipient markedly inhibited the growth of donor bone marrow granulocyte progenitor cells. On a third attempt, successful bone marrow engraftment was achieved following high-dose cyclophosphamide, which has previously been shown to be inhibitory to NK cells. We conclude that NK cell activity may play an important role in bone marrow failure as well as being responsible for at least some cases of aplastic anemia.

scholarly journals In vitro evidence for disappearance of erythroid progenitor T suppressor cells following allogeneic bone marrow transplantation for severe aplastic anemia

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 144-150
Author(s):  
KF Mangan ◽  
MT Mullaney ◽  
CS Rosenfeld ◽  
RK Shadduck
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
T Lymphocytes ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Before And After

In vitro coculture studies were performed in five patients with severe aplastic anemia (SAA) and their normal HLA-matched donors before and after allogeneic bone marrow transplantation (BMT) to determine whether the erythropoietic function of T cells is abnormal in this disorder. These coculture studies used fresh or cryopreserved marrow T lymphocytes with fresh or cryopreserved marrow T cell-depleted target cells. Four of five aplastic patients had little or no transfusion exposure before studies. The composite results showed that, in comparison to the erythropoietic effects of normal HLA-identical marrow T lymphocytes or engrafted T lymphocytes, T lymphocytes collected from the aplastic patients before BMT consistently suppressed or failed to support CFUE and BFUE growth optimally from autologous marrow, HLA- identical marrow, or engrafted aplastic T cell-depleted marrows. This T cell abnormality was not observed in four multiply transfused leukemics and three patients with myelodysplastic syndrome. Marker analyses of SAA marrow T lymphocytes performed before and after BMT suggested that the erythropoietic functional abnormality was due to abnormal marrow T cell composition reflecting an excess of activated Tac+, T3+, T11+ lymphocytes. Collectively, these in vitro studies provide firmer in vitro evidence implicating T cells in the pathogenesis of SAA. The erythropoietic T cells abnormalities in SAA are fully corrected by allogeneic BMT.

scholarly journals CD16- CD56+ natural killer cells after bone marrow transplantation

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3239-3244 ◽  
Author(s):  
R Jacobs ◽  
M Stoll ◽  
G Stratmann ◽  
R Leo ◽  
H Link ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune System ◽  
Bone Marrow Transplantation ◽  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Nk Cell ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes

Natural killer (NK) cells are phenotypically defined as lymphocytes expressing the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3- CD16- CD56+ NK cell subset has been described in normal individuals representing less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for their reconstitution of the immune system during follow-up after autologous or allogeneic bone marrow transplantation. In 35% of these patients, two different NK cell subsets, namely CD56+dim and CD56+bright cells, were observed. The mean duration of these two subsets after transplant was 4 months. Sixty-five percent of the patients exhibited an increased number of NK cells, but only the typical CD16+ CD56+dim population. The CD56+bright subpopulation represented a particular CD3- CD16- NK subset, with posttransplant frequencies up to 70% of all NK cells and 40% of peripheral blood lymphocytes, respectively. In contrast to normal CD56+dim NK cells, CD56+bright cells coexpressed the activation antigens p75 beta-chain of interleukin-2 receptor (IL-2R), CD2R, and CD26, but were negative for CD16. NK and antibody-dependent cellular cytotoxicity activity of CD56+bright cells was low compared with CD56+dim NK cells. But using IL-2 and interferon gamma, their cytotoxicity could be enhanced even more than in CD56+dim lymphocytes. These different subsets may reflect distinct activation or differentiation steps of NK cells during reconstitution of the immune system. Their differential response to IL-2 may be of functional importance for posttransplant cytokine therapy.

Sign in / Sign up

Export Citation Format

Share Document