HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death
Scott J. Brodie, … , Stanley R. Riddell, Lawrence Corey
Scott J. Brodie, … , Stanley R. Riddell, Lawrence Corey
Published May 15, 2000
Citation Information: J Clin Invest. 2000;105(10):1407-1417. https://doi.org/10.1172/JCI8707.
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Article

HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death

Abstract

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.

Authors

Scott J. Brodie, Bruce K. Patterson, Deborah A. Lewinsohn, Kurt Diem, David Spach, Phillip D. Greenberg, Stanley R. Riddell, Lawrence Corey

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Comparison of solution-phase PCR assays for the quantification of neo in...
Comparison of solution-phase PCR assays for the quantification of neo in lymph node mononuclear cells (filled symbols) and concurrent analysis of PBMC (open circles). Sample preparation, assay procedures, and controls are as described in Methods. For negative controls, lymph node and blood leukocytes were obtained 1 year previously from patient 1 and represent unmodified (neo-negative) CD8+ T cells. Data points denote mean ± SEM for neo and represent the end-point titer per microgram of CD8+ T-cell DNA. All samples were run in triplicate and all assays repeated at least twice.