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Alloantigen-stimulated anti-HIV activity
L A Pinto1, S Sharpe, D I Cohen
1Experimental Immunology Branch and Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Blood
|October 27, 1998
Summary
Alloantigen stimulation of immune cells from HIV-negative individuals generates CD8(+) T cells that inhibit HIV-1 replication. These cells and their secreted factors block diverse HIV-1 strains via a chemokine-independent pathway.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Studies suggest human leukocyte antigen (HLA) alloantigen immune responses may protect against HIV infection.
- Investigating the role of alloantigen-stimulated cells and their soluble factors in controlling HIV-1 replication.
Purpose of the Study:
- To determine if alloantigen-stimulated cell lines from HIV-negative individuals can inhibit HIV-1 replication.
- To characterize the mechanism of inhibition, including the role of soluble factors and chemokines.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) from HIV-negative donors were stimulated in vitro with allogeneic PBMC.
- Expanded CD8(+) T-cell lines were co-cultured with HIV-1-infected cells (PHA blasts or chronically infected cell lines).
- Supernatants from stimulated cell lines were tested for inhibitory activity; blocking experiments with anti-chemokine antibodies were performed.
Main Results:
- Alloantigen-stimulated CD8(+) T-cell lines inhibited HIV-1 replication in both autologous and heterologous PHA blasts.
- Supernatants from these cell lines also inhibited HIV-1 replication in PHA blasts and a chronically infected cell line.
- Inhibition occurred against both T-cell-tropic (T) and macrophage-tropic (M) HIV-1 isolates and was independent of beta-chemokines.
Conclusions:
- Alloantigen stimulation activates CD8(+) T cells in HIV-negative individuals, producing soluble factors that inhibit a broad spectrum of HIV-1 isolates.
- The inhibition mechanism is chemokine-independent, suggesting novel pathways for HIV-1 control.
- These findings highlight a potential immune-based strategy for HIV-1 intervention.