Functional role of interleukin-4 (IL-4) and IL-7 in the development of X-linked severe combined immunodeficiency.

Abstract

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.

• Authors: S Kumaki, N Ishii, M Minegishi, S Tsuchiya, D Cosman, K Sugamura, T Konno
• Journal: Blood (Blood) Vol. 93 Issue 2 Pg. 607-12 (Jan 15 1999) ISSN: 0006-4971 [Print] United States
• PMID: 9885222 (Publication Type: Case Reports, Journal Article)

Chemical References

• Interleukin-7
• Receptors, Interleukin-2
• Receptors, Interleukin-7
• Recombinant Proteins
• Interleukin-4
• Phosphotyrosine

Topics

• Genetic Linkage
• Humans
• Immunoblotting
• Immunosorbent Techniques
• Infant
• Interleukin-4 (pharmacology, physiology)
• Interleukin-7 (pharmacology, physiology)
• Leukemia, T-Cell
• Male
• Mutation
• Phosphotyrosine (analysis, metabolism)
• Receptors, Interleukin-2 (genetics)
• Receptors, Interleukin-7 (genetics)
• Recombinant Proteins
• Severe Combined Immunodeficiency (genetics)
• Signal Transduction
• T-Lymphocytes (metabolism)
• Transfection
• Tumor Cells, Cultured
• X Chromosome