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AIDS. 2002 Jul 5;16(10):1319-29.

Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: roles for cross-presentation and non-infectious HIV-1 virus.

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  • 1The Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York 10021, USA.

Abstract

BACKGROUND:

The CD4 T cells in mucosal subepithelia are the first cells to become infected during sexual transmission of HIV-1. Dendritic cells (DC) are located in the same area and are known to play a central role in antiviral immune responses. However, extensive viral replication, syncytia formation and cell death follows the interaction between T cells and DC previously exposed to HIV-1. Despite this, anti-HIV responses are generated that control viremia following acute infection.

OBJECTIVE:

The anti-HIV-1 cellular immune responses observed may be activated by sources other than productively infected DC. HIV-1 induces apoptosis both in cells it infects and in bystander cells. Furthermore, retroviral replication typically generates a predominance of defective particles. We tested whether DC exposed to antigen from either of these sources could elicit anti-HIV specific immune responses.

DESIGN AND METHODS:

Apoptotic or necrotic monocytes infected with vaccinia virus vectors encoding HIV antigens, a cell line with integrated HIV-1 and apoptotic CD4 T cells pulsed with non-infectious or infectious HIV-1 virus were used as sources of antigens to assess cross presentation by DC. Furthermore, direct DC presentation of antigen from non-infectious and infectious HIV-1 was examined.

RESULTS:

We find that dead cells expressing HIV-1 antigens as well as non-infectious HIV-1 particles can be acquired and processed by DC, leading to the activation, differentiation and expansion of viral antigen-specific CD4 and CD8 T cells from seropositive individuals.

CONCLUSIONS:

These sources of antigens may be critical for the generation and maintenance of anti-HIV-1 immunity by DC.

PMID:
12131208
[PubMed - indexed for MEDLINE]
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