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 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.

scholarly journals Anti-leukemia potential of interleukin-2 activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2250-2262 ◽  
Author(s):  
M Hauch ◽  
MV Gazzola ◽  
T Small ◽  
C Bordignon ◽  
L Barnett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Nk Cells ◽  
Natural Killer ◽  
Chronic Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Lytic Activity ◽  
Myelogenous Leukemia

Abstract The anti-leukemia potential of natural killer (NK) cells has been evaluated in 40 patients transplanted for chronic myelogenous leukemia (CML) to determine whether differences in NK cell function were correlated with subsequent leukemic relapse. Cells from patients and their donors were tested in 51Cr release assays against fully allogeneic CML targets and against cultured K562 targets; cells from 26 patients were tested against host-derived CML targets that were cryopreserved before transplantation. Cultured CML targets (K562) were highly susceptible to lysis by freshly isolated peripheral blood lymphocytes (PBL) and to a greater degree by PBL cultured in medium containing interleukin-2 (IL-2) in all assays performed. In contrast, noncultured CML targets were lysed only by IL-2-activated cells from a subset of patients. When present, lytic activity to CML targets was detectable as early as 3 weeks after bone marrow transplantation, and remained positive throughout the posttransplant period. Optimal lytic activity developed within the first week of culture and required greater than or equal to 250 U/mL of IL-2 in the culture medium. Lytic activity to fully allogeneic and host-derived CML targets appeared to be mediated by CD16+ and CD56+ cells but not by CD3+ cells. Lysis of allogeneic CML targets was variable, but patients could be divided into two groups: those with and those without lytic activity to the majority of targets tested. The basis for the differences in lytic activity could not be ascribed to target susceptibility to lysis, the proportion of NK cells in the cultures, or to the phenotype of the NK cell subsets in the cultures. When tested in parallel, the lytic activity of donor and recipient cultures against host-derived CML targets was highly correlated, suggesting that there may be inherent differences in the ability of NK cells to recognize CML targets. The risk of relapse for patients who failed to generate lytic activity against host-derived CML targets was significantly increased over that for patients with lytic activity against host leukemia. These data indicate that posttransplant immunotherapy with IL-2 designed to activate NK cells will likely augment the graft-versus-leukemia potential of the graft.

scholarly journals Anti-leukemia potential of interleukin-2 activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2250-2262 ◽  
Author(s):  
M Hauch ◽  
MV Gazzola ◽  
T Small ◽  
C Bordignon ◽  
L Barnett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Nk Cells ◽  
Natural Killer ◽  
Chronic Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Lytic Activity ◽  
Myelogenous Leukemia

The anti-leukemia potential of natural killer (NK) cells has been evaluated in 40 patients transplanted for chronic myelogenous leukemia (CML) to determine whether differences in NK cell function were correlated with subsequent leukemic relapse. Cells from patients and their donors were tested in 51Cr release assays against fully allogeneic CML targets and against cultured K562 targets; cells from 26 patients were tested against host-derived CML targets that were cryopreserved before transplantation. Cultured CML targets (K562) were highly susceptible to lysis by freshly isolated peripheral blood lymphocytes (PBL) and to a greater degree by PBL cultured in medium containing interleukin-2 (IL-2) in all assays performed. In contrast, noncultured CML targets were lysed only by IL-2-activated cells from a subset of patients. When present, lytic activity to CML targets was detectable as early as 3 weeks after bone marrow transplantation, and remained positive throughout the posttransplant period. Optimal lytic activity developed within the first week of culture and required greater than or equal to 250 U/mL of IL-2 in the culture medium. Lytic activity to fully allogeneic and host-derived CML targets appeared to be mediated by CD16+ and CD56+ cells but not by CD3+ cells. Lysis of allogeneic CML targets was variable, but patients could be divided into two groups: those with and those without lytic activity to the majority of targets tested. The basis for the differences in lytic activity could not be ascribed to target susceptibility to lysis, the proportion of NK cells in the cultures, or to the phenotype of the NK cell subsets in the cultures. When tested in parallel, the lytic activity of donor and recipient cultures against host-derived CML targets was highly correlated, suggesting that there may be inherent differences in the ability of NK cells to recognize CML targets. The risk of relapse for patients who failed to generate lytic activity against host-derived CML targets was significantly increased over that for patients with lytic activity against host leukemia. These data indicate that posttransplant immunotherapy with IL-2 designed to activate NK cells will likely augment the graft-versus-leukemia potential of the graft.

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 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.

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