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


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.
The Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York 10021, USA.
Marie
M
Larsson
Jean-Francois
JF
Fonteneau
Margareta
M
Lirvall
Patrick
P
Haslett
Jeffrey D
JD
Lifson
Nina
N
Bhardwaj
D017951:Antigen Presentation; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D008213:Lymphocyte Activation
D015488:HIV Antigens