We have analyzed the immune system in Stat5-deficient mice. Although Stat5a−/− splenocytes have a partial defect in anti-CD3-induced proliferation that can be overcome by high dose interleukin (IL)-2, we now demonstrate that defective proliferation in Stat5b−/− splenocytes cannot be corrected by this treatment. Interestingly, this finding may be at least partially explained by diminished expression of the IL-2 receptor β chain (IL-2Rβ), which is a component of the receptors for both IL-2 and IL-15, although other defects may also exist. Similar to the defect in proliferation in activated splenocytes, freshly isolated splenocytes from Stat5b−/− mice exhibited greatly diminished proliferation in response to IL-2 and IL-15. This results from both a decrease in the number and responsiveness of natural killer (NK) cells. Corresponding to the diminished proliferation, basal as well as IL-2– and IL-15–mediated boosting of NK cytolytic activity was also greatly diminished. These data indicate an essential nonredundant role for Stat5b for potent NK cell–mediated proliferation and cytolytic activity.
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7 December 1998
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December 07 1998
Stat5b Is Essential for Natural Killer Cell–mediated Proliferation and Cytolytic Activity
Kazunori Imada,
Kazunori Imada
From the *Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674; the ‡Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the §Ministry of Agriculture and Forestry (Verification Agency), Te Kuiti, New Zealand; and the ¶Dairy Science Group, AgResearch, Ruakura, Hamilton, New Zealand
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Eda T. Bloom,
Eda T. Bloom
From the *Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674; the ‡Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the §Ministry of Agriculture and Forestry (Verification Agency), Te Kuiti, New Zealand; and the ¶Dairy Science Group, AgResearch, Ruakura, Hamilton, New Zealand
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Hiroshi Nakajima,
Hiroshi Nakajima
From the *Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674; the ‡Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the §Ministry of Agriculture and Forestry (Verification Agency), Te Kuiti, New Zealand; and the ¶Dairy Science Group, AgResearch, Ruakura, Hamilton, New Zealand
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Judith A. Horvath-Arcidiacono,
Judith A. Horvath-Arcidiacono
From the *Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674; the ‡Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the §Ministry of Agriculture and Forestry (Verification Agency), Te Kuiti, New Zealand; and the ¶Dairy Science Group, AgResearch, Ruakura, Hamilton, New Zealand
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Garry B. Udy,
Garry B. Udy
From the *Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674; the ‡Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the §Ministry of Agriculture and Forestry (Verification Agency), Te Kuiti, New Zealand; and the ¶Dairy Science Group, AgResearch, Ruakura, Hamilton, New Zealand
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Helen W. Davey,
Helen W. Davey
From the *Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674; the ‡Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the §Ministry of Agriculture and Forestry (Verification Agency), Te Kuiti, New Zealand; and the ¶Dairy Science Group, AgResearch, Ruakura, Hamilton, New Zealand
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Warren J. Leonard
Warren J. Leonard
From the *Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674; the ‡Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the §Ministry of Agriculture and Forestry (Verification Agency), Te Kuiti, New Zealand; and the ¶Dairy Science Group, AgResearch, Ruakura, Hamilton, New Zealand
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Kazunori Imada
,
Eda T. Bloom
,
Hiroshi Nakajima
,
Judith A. Horvath-Arcidiacono
,
Garry B. Udy
,
Helen W. Davey
,
Warren J. Leonard
From the *Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674; the ‡Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the §Ministry of Agriculture and Forestry (Verification Agency), Te Kuiti, New Zealand; and the ¶Dairy Science Group, AgResearch, Ruakura, Hamilton, New Zealand
Address correspondence to Warren J. Leonard, Bldg. 10, Rm. 7N252, NIH, Bethesda, MD 20892-1674. Phone: 301-496-0098; Fax: 301-402-0971; E-mail: [email protected]
K. Imada was supported in part by a Japanese Society for the Promotion of Science research fellowship for Japanese biomedical and behavioral researchers at NIH and by the Sankyo Foundation of Life Science.
Received:
July 23 1998
Revision Received:
September 29 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (11): 2067–2074.
Article history
Received:
July 23 1998
Revision Received:
September 29 1998
Citation
Kazunori Imada, Eda T. Bloom, Hiroshi Nakajima, Judith A. Horvath-Arcidiacono, Garry B. Udy, Helen W. Davey, Warren J. Leonard; Stat5b Is Essential for Natural Killer Cell–mediated Proliferation and Cytolytic Activity . J Exp Med 7 December 1998; 188 (11): 2067–2074. doi: https://doi.org/10.1084/jem.188.11.2067
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