Cord blood natural killer cells are functionally and phenotypically immature but readily respond to interleukin-2 and interleukin-12

J. Gaddy, G. Risdon, Hal Broxmeyer

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Abstract

Human umbilical cord blood (CB) is being increasingly used both as an alternative to bone marrow to transplant children and for experimental insight into the ontogenic and maturational characteristics of blood cells. We studied the functional and phenotypic characteristics of CB natural killer (NK) cells because of the possibly important role such cells may play in a transplant setting and to gain insight into the little known ontogenic differences and maturational pathways of NK cells. It was found that CB NK lytic activity is usually deficient and that this deficiency cannot be fully explained by the presence of insufficient percentages of CD56+ cells. Although CD16+CD56+ and CD16-CD56+ NK cell subsets typical of adult peripheral blood (PB) are present, a significant population of CD16+CD56- cells also exists in CB. CB CD16+CD56- cells have little or no lytic capabilities; CB CD16+CD56+ cells vary in their lytic capabilities. Although a decreased ability to bind target cells may contribute to the deficient lyric activity of these CB NK cell subsets, studies suggest that other factors must also play a role. Short-term incubation with interleukin- 2 (IL-2) or interleukin-12 (IL-12) substantially increases the lytic capabilities of CB NK cells, and long-term incubations induce lymphokine- activated killer (LAK) cell generation. Cell depletion experiments show that activated CD56+ NK cells are responsible for the lytic activity of CB LAK cells. Flow cytometric analysis reveals that during LAK cell generation, CB undergoes phenotypic changes similar to those of PB except that CD16+CD56- cells are still present. These findings demonstrate that CB NK cells are functionally deficient and phenotypically different in comparison with PB NK cells, yet are responsive to IL-2 and IL-12 in the ability both to increase lyric activity and to undergo phenotypic change.

Original languageEnglish
Pages (from-to)527-536
Number of pages10
JournalJournal of Interferon and Cytokine Research
Volume15
Issue number6
StatePublished - 1995

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Interleukin-12
Fetal Blood
Natural Killer Cells
Interleukin-2
Blood Cells
Lymphokine-Activated Killer Cells
Transplants
Bone Marrow

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Virology

Cite this

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title = "Cord blood natural killer cells are functionally and phenotypically immature but readily respond to interleukin-2 and interleukin-12",
abstract = "Human umbilical cord blood (CB) is being increasingly used both as an alternative to bone marrow to transplant children and for experimental insight into the ontogenic and maturational characteristics of blood cells. We studied the functional and phenotypic characteristics of CB natural killer (NK) cells because of the possibly important role such cells may play in a transplant setting and to gain insight into the little known ontogenic differences and maturational pathways of NK cells. It was found that CB NK lytic activity is usually deficient and that this deficiency cannot be fully explained by the presence of insufficient percentages of CD56+ cells. Although CD16+CD56+ and CD16-CD56+ NK cell subsets typical of adult peripheral blood (PB) are present, a significant population of CD16+CD56- cells also exists in CB. CB CD16+CD56- cells have little or no lytic capabilities; CB CD16+CD56+ cells vary in their lytic capabilities. Although a decreased ability to bind target cells may contribute to the deficient lyric activity of these CB NK cell subsets, studies suggest that other factors must also play a role. Short-term incubation with interleukin- 2 (IL-2) or interleukin-12 (IL-12) substantially increases the lytic capabilities of CB NK cells, and long-term incubations induce lymphokine- activated killer (LAK) cell generation. Cell depletion experiments show that activated CD56+ NK cells are responsible for the lytic activity of CB LAK cells. Flow cytometric analysis reveals that during LAK cell generation, CB undergoes phenotypic changes similar to those of PB except that CD16+CD56- cells are still present. These findings demonstrate that CB NK cells are functionally deficient and phenotypically different in comparison with PB NK cells, yet are responsive to IL-2 and IL-12 in the ability both to increase lyric activity and to undergo phenotypic change.",
author = "J. Gaddy and G. Risdon and Hal Broxmeyer",
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T1 - Cord blood natural killer cells are functionally and phenotypically immature but readily respond to interleukin-2 and interleukin-12

AU - Gaddy, J.

AU - Risdon, G.

AU - Broxmeyer, Hal

PY - 1995

Y1 - 1995

N2 - Human umbilical cord blood (CB) is being increasingly used both as an alternative to bone marrow to transplant children and for experimental insight into the ontogenic and maturational characteristics of blood cells. We studied the functional and phenotypic characteristics of CB natural killer (NK) cells because of the possibly important role such cells may play in a transplant setting and to gain insight into the little known ontogenic differences and maturational pathways of NK cells. It was found that CB NK lytic activity is usually deficient and that this deficiency cannot be fully explained by the presence of insufficient percentages of CD56+ cells. Although CD16+CD56+ and CD16-CD56+ NK cell subsets typical of adult peripheral blood (PB) are present, a significant population of CD16+CD56- cells also exists in CB. CB CD16+CD56- cells have little or no lytic capabilities; CB CD16+CD56+ cells vary in their lytic capabilities. Although a decreased ability to bind target cells may contribute to the deficient lyric activity of these CB NK cell subsets, studies suggest that other factors must also play a role. Short-term incubation with interleukin- 2 (IL-2) or interleukin-12 (IL-12) substantially increases the lytic capabilities of CB NK cells, and long-term incubations induce lymphokine- activated killer (LAK) cell generation. Cell depletion experiments show that activated CD56+ NK cells are responsible for the lytic activity of CB LAK cells. Flow cytometric analysis reveals that during LAK cell generation, CB undergoes phenotypic changes similar to those of PB except that CD16+CD56- cells are still present. These findings demonstrate that CB NK cells are functionally deficient and phenotypically different in comparison with PB NK cells, yet are responsive to IL-2 and IL-12 in the ability both to increase lyric activity and to undergo phenotypic change.

AB - Human umbilical cord blood (CB) is being increasingly used both as an alternative to bone marrow to transplant children and for experimental insight into the ontogenic and maturational characteristics of blood cells. We studied the functional and phenotypic characteristics of CB natural killer (NK) cells because of the possibly important role such cells may play in a transplant setting and to gain insight into the little known ontogenic differences and maturational pathways of NK cells. It was found that CB NK lytic activity is usually deficient and that this deficiency cannot be fully explained by the presence of insufficient percentages of CD56+ cells. Although CD16+CD56+ and CD16-CD56+ NK cell subsets typical of adult peripheral blood (PB) are present, a significant population of CD16+CD56- cells also exists in CB. CB CD16+CD56- cells have little or no lytic capabilities; CB CD16+CD56+ cells vary in their lytic capabilities. Although a decreased ability to bind target cells may contribute to the deficient lyric activity of these CB NK cell subsets, studies suggest that other factors must also play a role. Short-term incubation with interleukin- 2 (IL-2) or interleukin-12 (IL-12) substantially increases the lytic capabilities of CB NK cells, and long-term incubations induce lymphokine- activated killer (LAK) cell generation. Cell depletion experiments show that activated CD56+ NK cells are responsible for the lytic activity of CB LAK cells. Flow cytometric analysis reveals that during LAK cell generation, CB undergoes phenotypic changes similar to those of PB except that CD16+CD56- cells are still present. These findings demonstrate that CB NK cells are functionally deficient and phenotypically different in comparison with PB NK cells, yet are responsive to IL-2 and IL-12 in the ability both to increase lyric activity and to undergo phenotypic change.

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