Correction of proliferative responses in purine nucleoside phosphorylase (PNP)-deficient T lymphocytes by retroviral-mediated PNP gene transfer and expression.

Journal Article (Journal Article)

Purine nucleoside phosphorylase (PNP; EC deficiency is associated with a fatal T cell immunodeficiency in children, a candidate condition for gene therapy by introduction of functional PNP sequences into either T lymphocytes or more primitive progenitor cells in the bone marrow. To test the effectiveness of PNP gene transfer in T lymphocytes, a retroviral vector (LmPSN-2) was designed and constructed to express the murine PNP cDNA under transcriptional regulation of the Moloney murine leukemia virus long terminal repeat. LmPSN-2 was first used to mediate gene transfer and expression of electrophoretically distinct murine PNP in normal (PNP-positive) human PBL. Peripheral blood leukocytes were then obtained from a PNP deficient patient and characterized phenotypically. Despite their paucity and general mitogenic unresponsiveness, T lymphocytes from this patient were successfully grown in culture by using anti-CD3 with rIL-2 and then transduced with LmPSN-2. Elevated PNP enzyme activity was observed in the transduced cell population. Mitogenic and allogeneic responses, normally depressed in PNP-deficient patients' cells, were partially corrected in the transduced cell population relative to nontransduced cells. These results suggest the possibility of effecting improved immunologic function in PNP-deficient T lymphoid cells by retroviral-mediated gene transfer as therapy for PNP deficiency.

Full Text

Duke Authors

Cited Authors

  • Nelson, DM; Butters, KA; Markert, ML; Reinsmoen, NL; McIvor, RS

Published Date

  • March 15, 1995

Published In

Volume / Issue

  • 154 / 6

Start / End Page

  • 3006 - 3014

PubMed ID

  • 7876563

International Standard Serial Number (ISSN)

  • 0022-1767


  • eng

Conference Location

  • United States