Functional role of interleukin-4 (IL-4) and IL-7 in the development of X-linked severe combined immunodeficiency.
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 gammac chain. The gammac 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 alpha (IL-7Ralpha) 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 gammac chain (A156V) isolated from an X-SCID patient and found that T cells expressing the mutant gammac chain were selectively impaired in their responses to IL-4 or IL-7 compared with the wild-type gammac 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 gammac chain is critical for T-cell development and plays an important role in the development of the X-SCID phenotype.
Kumaki
S
S
Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. kumakis@europa.idac.tohoku.ac.jp
Ishii
N
N
Minegishi
M
M
Tsuchiya
S
S
Cosman
D
D
Sugamura
K
K
Konno
T
T
D008040:Genetic Linkage; D006801:Humans; D015151:Immunoblotting; D007163:Immunosorbent Techniques; D007223:Infant; D015847:Interleukin-4 / Q000494:pharmacology / Q000502:physiology*; D015851:Interleukin-7 / Q000494:pharmacology / Q000502:physiology*; D015458:Leukemia, T-Cell; D008297:Male; D009154:Mutation; D019000:Phosphotyrosine / Q000032:analysis / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000235:genetics; D011994:Recombinant Proteins; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014960:X Chromosome
D015851:Interleukin-7; D015375:Receptors, Interleukin-2; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D015847:Interleukin-4; D019000:Phosphotyrosine