Rapid death of adoptively transferred T cells in acquired immunodeficiencysyndrome

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) p robably play the major role in controlling HIV replication. However, the va lue of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ pati ents has been limited: this contrasts with the success of CTL therapy in tr eating or preventing Epstein-Barr virus and cytomegalovirus disease after b one marrow transplantation (BMT). We investigated the fate of expanded HIV- specific CTL clones in vivo following adoptive transfer to a patient with a cquired immunodeficiency syndrome (AIDS). Two autologous Cn clones specific for HIV Gag and Pol were expanded to large numbers (>10(9)) in vitro and i nfused into an HIV-infected patient whose viral load was rising despite ant iretroviral therapy. The fate of one clone was monitored by staining periph eral blood mononuclear cells (PBMCs) with T-cell receptor-specific tetramer ic major histocompatibility complex (MHC)-peptide complexes. Although the C TL transfer was well tolerated, there were no significant changes in CD4 an d CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through a poptosis. Thus, the failure of adoptively transferred HIV-specific CTL to r educe virus load in AIDS may be due to rapid apoptosis of the infused cells , triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cel ls to in vivo apoptosis. (C) 1999 by The American Society of Hematology.