Enforced expression of Bcl-2 restores the number of NK cells, but does not rescue the impaired development of NKT cells or intraepithelial lymphocytes, in IL-2/IL-15 receptor beta-chain-deficient mice.
IL-2/IL-15Rbeta-deficient mice display impaired development of NK cells, NKT cells, and intraepithelial lymphocytes of the intestine and skin. To determine the role of survival signals mediated by IL-2/IL-15R in the development of these innate lymphocytes, we introduced a bcl-2 transgene into IL-2/IL-15Rbeta-deficient mice. Enforced expression of Bcl-2 restored the number of NK cells in IL-2/IL-15Rbeta-deficient mice, but the rescued NK cells showed no cytotoxic activity. The numbers of NKT cells and intestinal intraepithelial lymphocytes did not increase significantly, and skin intraepithelial lymphocytes remained undetectable in the bcl-2 transgenic IL-2/IL-15Rbeta-deficient mice. These results indicate an essential role of IL-2/IL-15R-mediated survival signals in the development of NK cells, but they also show that additional nonsurvival signals from IL-2/IL-15R are necessary for innate lymphocyte development.
Minagawa
Masahiro
M
Department of Dermatology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Niigata 951-8510, Japan.
Watanabe
Hisami
H
Miyaji
Chikako
C
Tomiyama
Katsuhiro
K
Shimura
Hideki
H
Ito
Akiko
A
Ito
Masaaki
M
Domen
Jos
J
Weissman
Irving L
IL
Kawai
Kazuhiro
K
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D012867:Skin / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019076:Transgenes / Q000276:immunology
C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D019253:Proto-Oncogene Proteins c-bcl-2; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2