Anti-HIV genetic treatment of antigen-specific human CD4 lymphocytes for adoptive immunotherapy of opportunistic infections in AIDS

Gene Therapy
F MancaG Palú

Abstract

HIV-1 infection results in the loss of CD4+ T helper lymphocytes which make up the immune repertoire. This leads to opportunistic infections that define AIDS. Here, we show that CD4 T cell lines from normal donors with specificity for different antigens can be rendered resistant to HIV-1 replication by retroviral transduction with an antisense vector directed to the HIV-1 tat gene. The genetic treatment did not affect the properties of antigen-specific CD4 lymphocytes such as proliferative response, lymphokine production and phenotypic markers. The HIV-1 challenge dose that resulted in productive infection was two to four logs higher for transduced cells as compared with control cells. Resistance was shown with the HXB2 strain, whose tat sequence was used to design the antisense gene, and with the SF2 strain, whose targeted tat sequence carries five nucleotide mismatches. Retroviral transduction was also performed on a Candida-specific T cell line from a seropositive individual. This line, derived from T cells infected in vivo, produced infectious virus when stimulated in vitro with antigen, but was no longer productive after transduction. In addition, a four log higher HIV-1 challenge dose was needed for a productive superinfe...Continue Reading

Citations

Oct 12, 2001·Immunology Letters·G Li PiraF Manca
Jun 22, 2002·Antiviral Research·Francesca GennariCristina Parolin
Aug 26, 1998·Immunology Today·S A PorcelliM B Brenner
Feb 26, 1999·Journal of Biotechnology·G PalùA Marcello
Jan 12, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·David S StrayerRoger J Pomerantz
Aug 10, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·M C JensenA Raubitschek
Mar 16, 2002·Gene Therapy·G PalùF Manca

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