Published May 1, 2008 - 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.105:1407–1417 (2000). doi:10.1172/JCI8707.
Citation for this expression of concern: J. Clin. Invest.118:1974 (2008). doi:10.1172/JCI8707EX1.
In the issue of May 15, 2000, we published a study by Scott J. Brodie and colleagues. According to the report issued by John T. Slattery, Vice Dean of Research and Graduate Education at the University of Washington in Seattle, Washington, “Dr. Brodie was found to have falsified images that appeared as Figure 5A in the publication. These images respectively appeared in JCI as representing neomycin gene–marked CD8+ cells before patient infusions, with neo-positive cells showing yellow-red fluorescence and neo-negative cells being purple-blue; in one unfunded NIH grant application labeled as cells harboring HIV DNA (PCR in situ hybridization for gag DNA); and in a second unfunded NIH grant application as depicting alveolar macrophages from HIV+ persons treated with LPS, tuberculin or HIV tat protein-stain for viral RNA. The University’s investigative committee concluded that two or more of these images was falsified.”
There is an ongoing investigation into potential scientific misconduct in the performance of this study, reportedly by the Office of Research Integrity. We will inform our readers of the outcome of this investigation when it is complete.