PREEMPTIVE CD8 T-CELL IMMUNOTHERAPY OF ACUTE CYTOMEGALOVIRUS-INFECTION PREVENTS LETHAL DISEASE, LIMITS THE BURDEN OF LATENT VIRAL GENOMES, AND REDUCES THE RISK OF VIRUS RECURRENCE

In the immunocompetent host, primary cytomegalovirus (CMV) infection i s resolved by the immune response without causing overt disease. The v iral genome, however, is not cleared but is maintained in a latent sta te that entails a risk of virus recurrence and consequent organ diseas e. By using murine CMV as a model, we have shown previously that multi ple organs harbor latent CMV and that reactivation occurs with an inci dence that is determined by the viral DNA load in the respective organ (M. J. Reddehase, M. Balthesen, M. Rapp, S. Jonjic, I. Pavic, and U. II. Koszinowski. J. Exp. Med. 179:185-193, 1994). This predicts that a therapeutic intervention capable of limiting the load of latent viral genome should also reduce the risk of virus recurrence. Here we demon strate the benefits and the Limits of a preemptive CD8 T-cell immunoth erapy of CMV infection in the immunocompromised bone marrow transplant ation recipient. Antiviral CD8 T cells prevented CMV disease and accel erated the resolution of productive infection. The therapy also result ed in a lower load of latent CMV DNA in organs and consequently reduce d the incidence of recurrence. The data thus provide a further support ing argument for clinical trials of preemptive cytoimmunotherapy of hu man CMV disease with CD8 T cells. However, CD8 T cells failed to clear the viral DNA. The therapy-susceptible portion of the DNA load differ ed between organs and was highest in the Lungs. The existence of an in variant, therapy-resistant load suggests a role for immune system evas ion mechanisms in the establishment of CMV latency.