LMO2and Gene Therapy for Severe Combined Immunodeficiency

Publisher Website
Google Scholar
Abstract
McCormack and Rabbitts (Feb. 26 issue)1 discuss the role of activation of the T-cell oncogene LMO2 in inducing clonal T-cell proliferation in two patients after gene therapy for X-linked severe combined immunodeficiency (SCID), a condition caused by mutation of the γc cytokine-receptor subunit gene. The authors point to a role of γc as a cofactor of clonal proliferation. However, there are no data to suggest that, as proposed, the expression of a CD25–γc interleukin-2–receptor complex by T-cell precursors will make these cells hypersensitive to interleukin-2, since signal transduction without the βR subunit of interleukin-2 is highly questionable.2 It is more likely that LMO2 and γc exert a synergistic effect in mediating T-cell growth. The mechanisms by which LMO2 triggers cell proliferation are also not necessarily homogeneous. Aberrant LMO2 expression in mice blocks T-cell differentiation at an immature, double-negative stage,1 whereas transgenic LMO2+ clones exhibit a mature phenotype,3 suggestive of a post-thymic role.