Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor γ chain

Kazuyuki Ohbo, Toshio Suda, Motohiro Hashiyama, Akio Mantani, Mika Ikebe, Kazuhisa Miyakawa, Mako Moriyama, Masataka Nakamura, Motoya Katsuki, Kiyoshi Takahashi, Ken Ichi Yamamura, Kazuo Sugamura

研究成果: Article査読

201 被引用数 (Scopus)

抄録

The interleukin-2 (IL-2) receptor γ chain is indispensable for IL-2-, IL- 4-, IL-7-, IL-9-, and IL-15-mediated signaling. Mutations of the human γ chain cause the X-linked severe combined immunodeficiency (XSCID), showing that T and natural killer cells absolutely require the γ chain for their development in humans. To elucidate the roles of the y chain in hematopoiesis, we have generated mice, by gene targeting, that express a form of the γ chain lacking the cytoplasmic region. Male mice carrying the truncated γ-chain mutant, which mimics mutations in patients with XSCID, showed a decrease in the number of lymphocytes and an increase in monocytes; the number of T cells was profoundly reduced and no natural killer cells were detected, which is similar to the characteristic of human XSCID. Unlike human XSCID, the levels of B cells were also reduced. In spite of the severe decrease in CD45R+/sIgM+ B cells, the level of IgM in serum of the 8-week- old mutant mice was higher than that of control littermates. Interestingly, the stem cell population with surface phenotypes of CD34, c-kit, and Sca-1 was significantly increased. Furthermore, the colony-forming assay showed that the mutant mice had 15-fold higher numbers of hematopoietic progenitor cells in the spleen as compared with that of controls. These results indicate that functional loss of the γ chain causes significant effects on the immunological system in mice.

本文言語English
ページ(範囲)956-967
ページ数12
ジャーナルBlood
87
3
DOI
出版ステータスPublished - 1996 2 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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