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IL-15

Insights from Characterizing IL-15-Deficient Mice

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Cytokine Knockouts

Part of the book series: Contemporary Immunology ((CONTIM))

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Summary

Interleukin-15 (IL-15) is a 4-helix bundle cytokine with similar biologic properties as IL-2, consistent with their shared receptor subunits. Specificity for IL-15 and IL-2 is provided by unique private a-chain subunits. Studies to date examining the biology of IL-15 have identified several roles for this cytokine in both the differentiation as well as function of immune cells. IL-15 is important for NK cell, NK-T-cell, CD8 T-cell, and intestinal epithelial lymphocyte (IEL) growth and function. Recently, overexpression of IL-15 in diseased tissue has provided evidence for a potential role for IL-15 in inflammation. Mice that are genetically deficient in IL-15 or its unique receptor subunit IL-15Ra have recently been generated. These mice provide us with valuable tools to address the importance of IL-15 in immune responses. This chapter focuses on studies with the IL-15 deficient mice to address specific roles for IL-15 in the generation and function of immune cells. Wherever applicable, comparisons are provided to studies in IL-15Ra deficient mice.

Analysis of IL-15 and IL-15Ra deficient mice has shown that IL-15 is a crucial factor for the maturation, survival, and activation of NK cells. Furthermore, IL-15 is important for the survival of NK-T cells, differentiation, and activation of IEL and dendritic epidermal T-cells (DETC). Although the generation of primary and memory CD8 T-cell responses were not compromised significantly in IL-15 deficient mice, IL-15 plays an important role in maintaining memory CD8 T-cell, but not memory CD4 T-cell, homeostasis. IL-15 is crucial for the long-term survival of memory CD8 T-cells and for the bystander proliferation of naïve CD8 T-cells. Furthermore, APC from both IL-15 and IL-I5Ra deficient mice are defective in both IFNy and NO production, suggesting that IL-15 is important for both innate (APC, NK) as well as adaptive immunity (CD8 T-cells). Characterization of the IL-15 deficient mice has also provided another surprising function of IL-15 in the survival of kidney epithelial cells. The chapter also provides a summary of in vivo inflammation experiments performed in IL-15 deficient mice to identify a potential role for IL-15 in inflammatory disease. Although IL-15 deficient mice have normal DTH and contact hypersensitivity responses, they are increasingly susceptible to colitis suggesting that IL-15 may play an anti-inflammatory role in gut responses. Based on these studies, IL-15 or its unique IL-15Ra chain could serve as targets for therapy in human disease.

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Authors
  1. Pallavur V. Sivakumar
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  2. Sandra N. Brown
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  3. Ananda W. Goldrath
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  4. Anne Renee Van der Vuurst de Vries
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  5. Joanne L. Viney
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  6. Mary K. Kennedy
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  1. University of Colorado Health Sciences Center, Denver, CO, USA

    Giamila Fantuzzi PhD

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Sivakumar, P.V., Brown, S.N., Goldrath, A.W., Van der Vuurst de Vries, A.R., Viney, J.L., Kennedy, M.K. (2003). IL-15. In: Fantuzzi, G. (eds) Cytokine Knockouts. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-405-4_17

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  • DOI: https://doi.org/10.1007/978-1-59259-405-4_17

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