Natural killer cell differentiation

Insights from knockout and transgenic mouse models and in vitro systems

Noelle Sevilir Williams, Jennifer Klem, Igor J. Puzanov, P. V. Sivakumar, John D. Schatzle, Michael Bennett, Vinay Kumar

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Abstract

In the last few years, the routine development of knockout and transgenic mice and the ease with which rare progenitor population scan be isolated from hematopoietic organs and cultured in vitro has facilitated significant advances in understanding the lineage and development of natural killer (NK) cells. Fluorescence activated cell sorter analyses have identified a common lymphoid progenitor capable of giving rise to NK, T, and B cells, confirming the lymphoid origin of NK cells. Knockout and transgenic mouse models have pointed to an absolutely critical role for signals sent through the interleukin (IL)-2/15 receptor β (CD122) chain and common γ (γc) chain for NK development. Such signals are likely relayed inside the cell by the tyrosine kinase Jak3, which associates with γc. Recently developed IL-15 and IL-15 receptor α knockout mice have pinpointed IL-15 as the mediator of this signal. Other mouse models have indicated an unexpected role for flt3 ligand in early NK-cell development as well as minor roles for stem cell factor and IL-7 in expanding NK-cell progenitor numbers. Finally, in vitro culture systems have proven useful in identifying the point in NK development at which each of these signals is critical.

Original languageEnglish (US)
Pages (from-to)47-61
Number of pages15
JournalImmunological Reviews
Volume165
StatePublished - Oct 1998

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Knockout Mice
Natural Killer Cells
Transgenic Mice
Cell Differentiation
Interleukin-15 Receptors
Interleukin-15
Lymphoid Progenitor Cells
Interleukin-7
Natural Killer T-Cells
Stem Cell Factor
Interleukin-2 Receptors
Protein-Tyrosine Kinases
B-Lymphocytes
Cell Count
Fluorescence
In Vitro Techniques
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Williams, N. S., Klem, J., Puzanov, I. J., Sivakumar, P. V., Schatzle, J. D., Bennett, M., & Kumar, V. (1998). Natural killer cell differentiation: Insights from knockout and transgenic mouse models and in vitro systems. Immunological Reviews, 165, 47-61.

Natural killer cell differentiation : Insights from knockout and transgenic mouse models and in vitro systems. / Williams, Noelle Sevilir; Klem, Jennifer; Puzanov, Igor J.; Sivakumar, P. V.; Schatzle, John D.; Bennett, Michael; Kumar, Vinay.

In: Immunological Reviews, Vol. 165, 10.1998, p. 47-61.

Research output: Contribution to journalArticle

Williams, NS, Klem, J, Puzanov, IJ, Sivakumar, PV, Schatzle, JD, Bennett, M & Kumar, V 1998, 'Natural killer cell differentiation: Insights from knockout and transgenic mouse models and in vitro systems', Immunological Reviews, vol. 165, pp. 47-61.
Williams, Noelle Sevilir ; Klem, Jennifer ; Puzanov, Igor J. ; Sivakumar, P. V. ; Schatzle, John D. ; Bennett, Michael ; Kumar, Vinay. / Natural killer cell differentiation : Insights from knockout and transgenic mouse models and in vitro systems. In: Immunological Reviews. 1998 ; Vol. 165. pp. 47-61.
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