Bovine natural killer cells acquire cytotoxic/effector activity following activation with IL-12/15 and reduce Mycobacterium bovis BCG in infected macrophages

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Abstract

Bovine natural killer (NK) cells were recently identified by positive selection of a NK cell-activating receptor p46 (NKp46)+ CD3 - lymphocyte population, which expresses CD25 and CD8 and lyses tumor cell lines following stimulation with recombinant interleukin-2. In the current work, we characterize the cytotoxic/effector potential of a CD3 -CD8-CD11b- population isolated through negative selection of bovine peripheral blood leukocytes. This population is CD25loCD62hi when isolated and becomes CD25 hiCD62Llo following cytokine stimulation. Activated bovine NK cells increase expression of granulysin, interferon-γ, and perforin and have cytotoxic activity against human tumor cells and Mycobacterium bovis bacillus Calmette-Guerin-infected alveolar and monocyte-derived macrophages. Expression of a bovine homologue of the CD56 neural adhesion molecule expressed by human NK cells was detected in mRNA from brain tissue but was not detected in peripheral blood mononuclear cells or purified NK cell mRNA. Analysis of mRNA from nonstimulated peripheral blood NK cells demonstrates the constitutive expression of homologues of human NK receptors NKp46, CD244, and CD94 and the granule proteins granulysin and perforin. Phorbol ester-stimulated CD8 + T cells also expressed CD244 and CD94, and CD4+ T cells expressed CD94. These NK cell receptors bearing T lymphocytes may represent memory subsets characterized in humans. The results of these studies demonstrate that bovine NK cells may play an important role in the innate immune responses of cattle.

Original languageEnglish (US)
Pages (from-to)71-79
Number of pages9
JournalJournal of Leukocyte Biology
Volume79
Issue number1
DOIs
StatePublished - Jan 2006

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Interleukin-15
Interleukin-12
Mycobacterium bovis
Natural Killer Cells
Macrophages
Natural Killer Cell Receptors
Perforin
T-Lymphocytes
Messenger RNA
Natural Cytotoxicity Triggering Receptor 1
Blood Cells
Population
Phorbol Esters
Tumor Cell Line
Innate Immunity
Human Activities
Interferons
Interleukin-2
Leukocytes
Lymphocytes

Keywords

  • Cytotoxic granule proteins
  • Natural killer receptors
  • Tuberculosis

ASJC Scopus subject areas

  • Cell Biology

Cite this

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title = "Bovine natural killer cells acquire cytotoxic/effector activity following activation with IL-12/15 and reduce Mycobacterium bovis BCG in infected macrophages",
abstract = "Bovine natural killer (NK) cells were recently identified by positive selection of a NK cell-activating receptor p46 (NKp46)+ CD3 - lymphocyte population, which expresses CD25 and CD8 and lyses tumor cell lines following stimulation with recombinant interleukin-2. In the current work, we characterize the cytotoxic/effector potential of a CD3 -CD8-CD11b- population isolated through negative selection of bovine peripheral blood leukocytes. This population is CD25loCD62hi when isolated and becomes CD25 hiCD62Llo following cytokine stimulation. Activated bovine NK cells increase expression of granulysin, interferon-γ, and perforin and have cytotoxic activity against human tumor cells and Mycobacterium bovis bacillus Calmette-Guerin-infected alveolar and monocyte-derived macrophages. Expression of a bovine homologue of the CD56 neural adhesion molecule expressed by human NK cells was detected in mRNA from brain tissue but was not detected in peripheral blood mononuclear cells or purified NK cell mRNA. Analysis of mRNA from nonstimulated peripheral blood NK cells demonstrates the constitutive expression of homologues of human NK receptors NKp46, CD244, and CD94 and the granule proteins granulysin and perforin. Phorbol ester-stimulated CD8 + T cells also expressed CD244 and CD94, and CD4+ T cells expressed CD94. These NK cell receptors bearing T lymphocytes may represent memory subsets characterized in humans. The results of these studies demonstrate that bovine NK cells may play an important role in the innate immune responses of cattle.",
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