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Cell-cell interactions regulate dendritic cell-dependent HIV-1 production in CD4+ T lymphocytes
L M Pinchuk1, P S Polacino, M B Agy
1Regional Primate Research Center, University of Washington Medical Center, Seattle 98195, USA.
Advances in Experimental Medicine and Biology
|January 1, 1995
Summary
Blood dendritic cells (DCs) facilitate HIV-1 transmission to CD4+ T cells. This DC-mediated process involves specific molecular interactions, highlighting potential therapeutic targets for blocking HIV spread.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Dendritic cells (DCs) play a crucial role in immune responses and pathogen transmission.
- Understanding the mechanisms of HIV-1 transmission is vital for developing effective interventions.
Purpose of the Study:
- To investigate the role of blood dendritic cells (DCs) in HIV-1 transmission between infected and uninfected CD4+ T cells.
- To identify accessory molecules involved in DC-mediated HIV-1 transmission.
Main Methods:
- Utilized monoclonal antibodies (mAbs) to block or enhance specific molecular interactions.
- Assessed DC infectability and their role in promoting transmission.
- Investigated the effects of blocking agents like CTLA4Ig.
Main Results:
- Blood DCs promoted HIV-1 transmission to CD4+ T cells but were not infectable themselves.
- DC-mediated transmission was inhibited by antibodies to CD4 and MHC class II.
- Antibodies to CD40 on DCs or CD28 on T cells enhanced transmission.
- Infection was inhibited by anti-CD80 and CTLA4Ig, which also blocked CD40-induced augmentation.
- CD40 activation upregulated CD80 and CD86 expression on DCs.
Conclusions:
- The interaction between CD40-CD40 ligand and CD28-CD80/B7-2 pathways on DCs and T cells is implicated in HIV-1 transmission.
- These molecular dialogues represent potential targets for therapeutic strategies against HIV infection.