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Blood, Vol. 93 No. 2 (January 15), 1999:
pp. 607-612
Functional Role of Interleukin-4 (IL-4) and IL-7 in the Development
of X-Linked Severe Combined Immunodeficiency
Satoru Kumaki,
Naoto Ishii,
Masayoshi Minegishi,
Shigeru Tsuchiya,
David Cosman,
Kazuo Sugamura, and
Tasuke Konno
From the Department of Pediatric Oncology, Institute of Development,
Aging and Cancer, Tohoku University, Sendai, Japan; the Department of
Immunology, Tohoku University School of Medicine, Sendai, Japan; and
the Department of Molecular Biology, Immunex Research and Development
Corp, Seattle, WA.
X-linked severe combined immunodeficiency (X-SCID) is characterized
by an absent or diminished number of T cells and natural-killer (NK)
cells with a normal or elevated number of B cells, and results from
mutations of the  c chain. The c chain is shared by interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15 receptors. Recently, a survival signal through the IL-7 receptor  (IL-7R) chain was shown to be
important for T-cell development in mice and was suggested to
contribute to the X-SCID phenotype. In the present study, we examined
function of a mutant c chain (A156V) isolated from an X-SCID patient
and found that T cells expressing the mutant c chain were
selectively impaired in their responses to IL-4 or IL-7 compared with
the wild-type c chain expressing cells although responses to IL-2 or
IL-15 were relatively maintained. The result shows that IL-4-
and/or IL-7-induced signaling through the c chain is
critical for T-cell development and plays an important role in the
development of the X-SCID phenotype.
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