Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain.

JP DiSanto, W Müller, D Guy-Grand… - Proceedings of the …, 1995 - National Acad Sciences
JP DiSanto, W Müller, D Guy-Grand, A Fischer, K Rajewsky
Proceedings of the National Academy of Sciences, 1995National Acad Sciences
The interleukin 2 receptor gamma chain (IL-2R gamma) is a component of the receptors for
IL-2, IL-4, IL-7, and IL-15. Mutations in IL-2R gamma in man appear responsible for the X
chromosome-linked immunodeficiency SCIDX1, characterized by a defect in T-cell and
natural killer (NK)-cell differentiation with the presence of poorly functioning B cells. To
explore at which level IL-2R gamma affects lymphoid development in vivo, we have
analyzed mice derived from embryonic stem (ES) cells with mutant IL-2R gamma loci …
The interleukin 2 receptor gamma chain (IL-2R gamma) is a component of the receptors for IL-2, IL-4, IL-7, and IL-15. Mutations in IL-2R gamma in man appear responsible for the X chromosome-linked immunodeficiency SCIDX1, characterized by a defect in T-cell and natural killer (NK)-cell differentiation with the presence of poorly functioning B cells. To explore at which level IL-2R gamma affects lymphoid development in vivo, we have analyzed mice derived from embryonic stem (ES) cells with mutant IL-2R gamma loci generated by Cre/loxP-mediated recombination. In the peripheral blood of chimeric animals, lymphoid cells derived from IL-2R gamma- ES cells were not detected, although control ES cells carrying an IL-2R gamma gene with embedded loxP sites gave rise to T-, B-, and NK-cell lineages. Germline IL-2R gamma-deficient male animals, however, developed some mature splenic B and T cells, although the absolute number of lymphocytes was almost 10-fold reduced. In contrast, there was a complete disappearance of NK cells (over 350-fold reduction). Development of gut-associated intraepithelial lymphocytes was also severely diminished, and Peyer's patches were not detected. In vitro mitogenic responses of thymocytes, IL-4-directed immunoglobulin class switch of splenocytes, and NK activity were defective. Thus, IL-2R gamma facilitates mainstream B- and T-cell generation and function and also appears to be essential for NK-cell development.
National Acad Sciences