Rational reconstitution of the immune repertoire in AIDS with autologous, antigen-specific, in vitro-expanded CD4 lymphocytes.

HIV infection leads to decrease of CD4 lymphocytes. In particular, loss of CD4 cells specific for opportunistic pathogens results in active opportunistic infections, that are the chief cause of morbidity and mortality in AIDS. Highly active anti-retroviral therapy (HAART) has been shown to have dramatic effects in a large fraction of treated individuals, such as decrease of viral load and increase of CD4 cells. It has not been clearly established, though, whether CD4 cells that appear during HAART represent a functional repertoire (i.e. a CD4 repertoire that encompasses all specificities, including T-cells responding to opportunistic pathogens, as in immunocompetent individuals) or an amplified mirror image of a defective repertoire. Therefore we propose that the immune repertoire can be reconstituted with autologous CD4 lymphocytes collected at early stages of infection, selected for specificity for opportunistic pathogens, expanded and stored for future use when laboratory or clinical signs indicate a depletion of antigen-specific CD4 cells. Since the reinfused CD4 cells are themselves susceptible to HIV infection-replication, we suggest that in vitro gene therapy of these cells may confer a genetic resistance that is permanently maintained in these cells.