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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1407-1417
Number of pages11
JournalJournal of Clinical Investigation
Volume105
Issue number10
StatePublished - May 2000
Externally publishedYes

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Cytotoxic T-Lymphocytes
Cell Death
Lymph Nodes
HIV
Granzymes
CC Chemokines
Virus Replication
CCR5 Receptors
Genes
Viral Load
Clone Cells
RNA
Ligands
T-Lymphocytes
Phenotype
Antigens

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Brodie, S. J., Patterson, B. K., Lewinsohn, D., Diem, K., Spach, D., Greenberg, P. D., ... Corey, L. (2000). HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death. Journal of Clinical Investigation, 105(10), 1407-1417.

HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death. / Brodie, Scott J.; Patterson, Bruce K.; Lewinsohn, Deborah; Diem, Kurt; Spach, David; Greenberg, Phillip D.; Riddell, Stanley R.; Corey, Lawrence.

In: Journal of Clinical Investigation, Vol. 105, No. 10, 05.2000, p. 1407-1417.

Research output: Contribution to journalArticle

Brodie, SJ, Patterson, BK, Lewinsohn, D, Diem, K, Spach, D, Greenberg, PD, Riddell, SR & Corey, L 2000, 'HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death', Journal of Clinical Investigation, vol. 105, no. 10, pp. 1407-1417.
Brodie, Scott J. ; Patterson, Bruce K. ; Lewinsohn, Deborah ; Diem, Kurt ; Spach, David ; Greenberg, Phillip D. ; Riddell, Stanley R. ; Corey, Lawrence. / HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death. In: Journal of Clinical Investigation. 2000 ; Vol. 105, No. 10. pp. 1407-1417.
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