ANTI-HIV GENETIC TREATMENT OF ANTIGEN-SPECIFIC HUMAN CD4 LYMPHOCYTES FOR ADOPTIVE IMMUNOTHERAPY OF OPPORTUNISTIC INFECTIONS IN AIDS

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 dono rs with specificity for different antigens can be rendered resistant t o HIV-1 replication by retroviral transduction with an antisense vecto r directed to the HIV-1 tat gene. The genetic treatment did not affect the properties of antigen-specific CD4 lymphocytes such as proliferat ive response, lymphokine production and phenotypic markers. The HIV-1 challenge dose that resulted in productive infection was two to four l ogs higher for transduced cells as compared with control cells. Resist ance was shown with the HXB2 strain, whose tat sequence was used to de sign the antisense gene, and with the SF3 strain, whose targeted tat s equence carries five nucleotide mismatches. Retroviral transduction wa s also performed on a Candida-specific T cell line from a seropositive individual. This line, derived from T cells infected in vivo, produce d infectious virus when stimulated in vitro with antigen, but was no l onger productive after transduction. In addition, a four log higher HI V-1 challenge dose was needed for a productive superinfection of this T cell line. The production of an antigen-specific CD4 T cells resista nt to HIV-1 replication to be used in adoptive immunotherapy of opport unistic infections may represent a new form of gene therapy of AIDS.