Lymphold reconstitution in X-linked severe combined immunodeficient mice by retrovirus-mediated gene transfer

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The cytokine receptor common gamma chain (γc) plays a pivotal role in transmitting multiple interleukin signals. Its gene mutations cause profound lymphoid maldevelopment, a disorder known as X-linked severe combined immunodeficiency (X-SLID). Without successful bone marrow transplantation, affected patients would die in infancy or early childhood due to severe and recurrent infections. Therefore, development of gene therapy strategies has been awaited for those without suitable marrow donors. We constructed a retrovirus vector carrying the γc and the enhanced green fluorescent protein (EGFP) genes for a preclinical study with a murine X-SCID model. After transduction of X-SCID bone marrow and infusion into myeloablated X-SCID recipients, robust lymphoid reconstitution was observed in all the examined lymphocyte subsets such as CD4+-T, CD8+-T, B and NK cells. A long-term EGFP expression was demonstrated in both lymphoid and myeloid cells, suggesting that this type of vector is useful in evaluating regimens of stem cell-directed gene therapy.
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