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 opportunis tic infections, that are the chief cause of morbidity and mortality in AIDS . Highly active anti-retroviral therapy (HAART) has been shown to have dram atic effects in a large fraction of treated individuals, such as decrease o f 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, incl uding T-cells responding to opportunistic pathogens, as in immunocompetent individuals) or an amplified mirror image of a defective repertoire. Theref ore we propose that the immune repertoire can be reconstituted with autolog ous CD4 lymphocytes collected at early stages of infection, selected for sp ecificity for opportunistic pathogens, expanded and stored for future use w hen laboratory or clinical signs indicate a depletion of antigen-specific C D4 cells. Since the reinfused CD4 cells are themselves susceptible to HIV i nfection-replication, we suggest that in vitro gene therapy of these cells may confer a genetic resistance that is permanently maintained in these cel ls. (C) 1999 Elsevier Science B.V. All rights reserved.