Prolongation of adenoviral transgene expression in mouse liver by T lymphocyte subset depletion.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Prolongation of adenoviral transgene expression in mouse liver by T lymphocyte subset depletion.

Gene Ther. 1996 Jan;3(1):4-12. Unique Identifier : AIDSLINE MED/97083332
DeMatteo RP; Markmann JF; Kozarsky KF; Barker CF; Raper SE; Institute for Human Gene Therapy, University of Pennsylvania Medical; Center, Philadelphia, USA.

Abstract: Although first generation recombinant adenoviruses are efficient vehicles for gene transfer, their immunogenicity precludes long-term persistence. We show that adenoviral transgene expression in the liver of normal mice is prolonged from a baseline of less than 2 weeks to 7 weeks by depleting CD4+ T lymphocytes with thymectomy and a 3-day course of anti-CD4 monoclonal antibody or by nonselectively depleting T cells with a single dose of anti-thymocyte serum (ATS). Transgene expression persisted despite the development of an antiviral humoral immune response by 3 weeks after virus administration. In vitro assays of T lymphocyte function revealed an initial diminished capacity to proliferate in the presence of adenoviral antigens in animals depleted of CD4+ T cells or given anti-thymocyte serum. Eventual loss of recombinant gene expression coincided with the development of adenovirus-specific cytotoxic T lymphocyte activity in vitro. Immunosuppression provides a useful experimental tool to elucidate the immunobiology of recombinant adenoviruses and may have clinical application to adenovirus-mediated gene therapy.

Keywords: *Adenoviruses, Human/IMMUNOLOGY *CD4-Positive T-Lymphocytes/IMMUNOLOGY *Genetic Vectors/IMMUNOLOGY *Lymphocyte Depletion
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