DEFECTIVE LYMPHOID DEVELOPMENT IN MICE LACKING EXPRESSION OF THE COMMON CYTOKINE RECEPTOR-GAMMA CHAIN

The common gamma chain (gamma(c)) of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors is defective in hu mans with XSCID. Mice lacking gamma(c) expression had hypoplastic thymuses; the thymocytes responded to gamma(c)-independent mitogens, but not gamma(c)-dependent stimuli. Splenic T cells were diminished at 3 weeks of age, but CD4+ T cells markedly increased by 4 weeks. B cells were greatly diminished, in contrast with the situation in XSCID. NK cells, gamma delta intestinal intraepithelial lymphocytes, dendritic epidermal T cells, peripheral lymph nodes, and gut-associated lymphoid tissue were absent. These findings underscore the importance of gamma(c) in lymphoid development. Moreover, differences in humans and mice lacking ye expression indicate species-specific differences in the roles of gamma(c)-dependent cytokines or in the existence of redundant pathways. These mice provide an important model for studying the pathophysiology of and gene therapy for human XSCID.