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Titolo:
COMPARISON OF NATURAL-KILLER ACTIVITY OF HUMAN BONE-MARROW AND BLOOD-CELLS IN CULTURES CONTAINING IL-2,IL-7 AND IL-12
Autore:
WONG EK; EAVES C; KLINGEMANN HG;
Indirizzi:
UNIV BRITISH COLUMBIA,TERRY FOX LAB,601 W 10TH AVE VANCOUVER BC V5Z 1L3 CANADA UNIV BRITISH COLUMBIA,TERRY FOX LAB VANCOUVER BC V5Z 1L3 CANADA UNIV BRITISH COLUMBIA,LEUKEMIA BONE MARROW TRANSPLANT PROGRAM BRITISHC VANCOUVER BC V5Z 1M9 CANADA UNIV BRITISH COLUMBIA,DIV HEMATOL VANCOUVER BC V5Z 1M9 CANADA UNIV BRITISH COLUMBIA,BRITISH COLUMBIA CANC AGCY VANCOUVER BC V5Z 1M9CANADA UNIV BRITISH COLUMBIA,DEPT EXPT PATHOL & LAB MED VANCOUVER BC V5Z 1M9CANADA UNIV BRITISH COLUMBIA,DEPT MED GENET VANCOUVER BC V5Z 1M9 CANADA UNIV BRITISH COLUMBIA,DEPT MED VANCOUVER BC V5Z 1M9 CANADA
Titolo Testata:
Bone marrow transplantation
fascicolo: 1, volume: 18, anno: 1996,
pagine: 63 - 71
SICI:
0268-3369(1996)18:1<63:CONAOH>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE MYELOID-LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; LONG-TERM CULTURE; PERIPHERAL-BLOOD; FIRST REMISSION; STEM-CELLS; TRANSPLANTATION; INTERLEUKIN-2; GENERATION; PROLIFERATION;
Keywords:
INTERLEUKIN-2; ACUTE MYELOGENOUS LEUKEMIA; PURGING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
E.K. Wong et al., "COMPARISON OF NATURAL-KILLER ACTIVITY OF HUMAN BONE-MARROW AND BLOOD-CELLS IN CULTURES CONTAINING IL-2,IL-7 AND IL-12", Bone marrow transplantation, 18(1), 1996, pp. 63-71

Abstract

Previous studies have suggested that autologous bone marrow or mobilized peripheral blood progenitor cell transplants activated by prior culture of the cells in IL-2 may capture some of the beneficial graft-versus-leukemia effects obtained with unmanipulated allogeneic, but not autologous, transplants. To investigate ways of improving this approach, we have compared the ability of two other immunomodulating cytokines, IL-7 and IL-12, either alone or in combination with IL-2, to stimulate human bone marrow cells (BMC) or peripheral blood cells (PBC) to acquire the potential to lyse K562 or Daudi cells. For these studies, we measured the cytotoxic activity of BMC or PBC both before and at theend of their incubation with various cytokine(s) using a standard (51)-chromium release assay. Results suggest that IL-2 at optimal concentration induces cytotoxicity significantly higher than IL-7 or IL-12 when tested alone. At optimal concentration, the combination of IL-2 andIL-12 showed a synergistic effect for BMC. Such a synergistic effect could be observed for PBC only when suboptimal concentrations of IL-2 were used. In addition, the ability of the hematopoietic cells to reduce the number of K562 cells remaining at the end of various culture periods in the presence of the cytokines was measured. This was made possible by the use of a G418-resistant K562 cell line which could, in contrast to normal human BMC or PBC, form colonies that were detectable after 1 week in methylcellulose cultures containing the neomycin analog G418. Normal human PBC, stimulated by either IL-7 or IL-12 alone effectively suppressed K562 proliferation in both of these assays, whereas no activity could be detected when BMC were incubated under the sameconditions. On the other hand, cells from both sources displayed anti-leukemic activity when incubated with IL-2 and IL-12 together, although IL-2/IL-12-activated PBC suppressed the growth of co-cultivated K562-neo(r) cells about eight-fold more efficiently than IL-2/IL-12-activated BMC. Cryopreservation and subsequent stimulation of BMC and PBC with cytokines did not cause a significant decrease in cytotoxicity or their ability to inhibit the growth of co-cultivated K562 cells compared to fresh cells. However, the synergistic effect observed with the combination of IL-2/IL-12 was no longer detectable for BMC. These results suggest that (1) PBC are superior to BMC with respect to developingeffective natural killer (NK) activity after culture in cytokines andthat, (2) the combination of IL-2 and IL-12 may be more effective than IL-2 alone to inhibit proliferation/growth of K562 cells.

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Documento generato il 28/01/20 alle ore 21:00:04