First published September 1, 2010 - More info
We have tracked the in vivo migration and have identified in vivo correlates of cytotoxic T-lymphocyte (CTL) activity in HIV-seropositive subjects infused with autologous gene-marked CD8+ HIV-specific CTL. The number of circulating gene-marked CTL ranged from 1.6 to 3.5% shortly after infusion to less than 0.5% 2 weeks later. Gene-marked CTL were present in the lymph node at 4.5- to 11-fold excess and colocalized within parafollicular regions of the lymph node adjacent to cells expressing HIV tat fusion transcripts, a correlate of virus replication. The CTL clones expressed the CCR5 receptor and localized among HIV-infected cells expressing the ligands MIP-1α and MIP-1β, CC-chemokines produced at sites of virus replication. Aggregates of apoptotic cells and cells expressing granzyme-B localized within these same sites. In contrast, lymph node sections from untreated HIV-seropositive subjects, all with significant viral burden (> 50,000 HIV RNA copies/mL plasma), showed no CC-chemokine expression and exhibited only sporadic and randomly distributed cells expressing granzymes and/or apoptotic cells. These studies show that the infused CTL specifically migrate to sites of HIV replication and retain their antigen-specific cytolytic potential. Moreover, these studies provide a methodology that will facilitate studies of both the magnitude and functional phenotype of Ag-specific CD8+ T cells in vivo.
Scott J. Brodie, Bruce K. Patterson, Deborah A. Lewinsohn, Kurt Diem, David Spach, Phillip D. Greenberg, Stanley R. Riddell, Lawrence Corey
Original citation: J Clin Invest. 2000;105(10):1407–1417. doi:10.1172/JCI8707.
Citation for this erratum: J Clin Invest. 2010;120(9):3401. doi:10.1172/JCI8707R1.
Because of the falsification of one figure, Figure 5a, the co-authors of the article “HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death,“ published in 2000;105(10):1407–1417, have agreed to retract that article subsequent to the ORI findings of May 5, 2010 (Federal Register. 2010;75:24703–24704). Author Scott J. Brodie dissents from the co-authors’ decision.