Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain.
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.
Institut National de la Santé et de la Recherche Médicale, Unité 132, Hôpital Necker-Enfants Malades, Paris, France.
J P
JP
DiSanto
W
W
Müller
D
D
Guy-Grand
A
A
Fischer
K
K
Rajewsky
D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells; D002678:Chimera; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007421:Intestine, Small / Q000033:anatomy & histology / Q000276:immunology; D008208:Lymphatic System / Q000254:growth & development* / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010581:Peyer's Patches / Q000033:anatomy & histology; D015375:Receptors, Interleukin-2 / Q000235:genetics* / Q000276:immunology; D017384:Sequence Deletion; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013234:Stem Cells; D013950:Thymus Gland / Q000166:cytology; D014960:X Chromosome / Q000235:genetics*
D015375:Receptors, Interleukin-2