CORRECTION OF INTERLEUKIN-2 RECEPTOR FUNCTION IN X-SCID LYMPHOBLASTOID-CELLS BY RETROVIRALLY MEDIATED TRANSFER OF THE GAMMA(C) GENE

X-SCID, the most common form of human SCID, is due to mutations in the common gamma chain gene (gamma(c)) that encodes an essential componen t of the cytokine receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9 , and IL-15. Activation of the Janus family tyrosine kinases Jak1 and Jak3 is necessary for appropriate signalling through the IL-2 receptor (IL-2R). Neither Jak1 nor Jak3 was phosphorylated after IL-2 stimulat ion of an Epstein-Barr virus-transformed cell line (LCL) from an X-SCI D patient with a gamma(c) null mutation. However, we now show that app ropriate IL-2R function can be restored in an X-SCID LCL by transducti on of a wild-type gamma(c) gene. A retroviral vector, G1 gamma(c)SvNa, was constructed and produced in the PG13 packaging line. Transduced X -SCID LCL expressed the G1 gamma(c)SvNa transcript. IL-2 stimulation o f the transduced cell line resulted in appropriate tyrosine phosporyla tion of both Jak1 and Jak3. Thus, retroviral-mediated transduction of normal gamma(c) can reconstitute downstream signalling through the IL- 2R in X-SCID cell lines, suggesting that gene therapy may be a treatme nt for this disease. (C) 1996 by The American Society of Hematology.