J. Exp. Med., Volume 188, Number 11, December 7, 1998 2067-2074

Stat5b Is Essential for Natural Killer Cell-mediated Proliferation and Cytolytic Activity

By Kazunori Imada,^* Eda T. Bloom, Hiroshi Nakajima,^* Judith A. Horvath-Arcidiacono, Garry B. Udy,^§ Helen W. Davey,^¶ and 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

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  chain (IL-2R), 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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