Immunopathological role of IL-7 in the development of X-linked Severe Combined Immunodeficiency (X-SCID)

X-SCID is characterized by absent or diminished T cells and NK cells with normal numbers of B cells and results from mutations in the γ chain, which is shared by IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. Recently, survival signals through IL-7R were demonstrated to be important for T cell development in mice. However, in humans, it is not clear which cytokine plays a crucial role in T cell development and contributes to the X-SCID phenotype. We examined function of a mutant γ chain (Ala156Pro) isolated from an atypical X-SCID patient with normal NK activity. The mutant γ chain was stably transfected into a T cell line together with IL-7R. The transfectants failed to respond to IL-7 at lower concentrations although they responded to IL-2 and IL-15 comparably to the wild type γ chain expressing clones. The binding affinity of IL-7 to the transfectants expressing the mutant γ chain is 5-6 fold lower than that to the wild type γ chain expressing clones. These results suggest that IL-7-induced signals through the γ chain are critical for T cell development and play an important role in the development of the X-SCID phenotype.