Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: Roles for cross-presentation and non-infectious HIV-1 virus
2002 (English)In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 16, no 10, 1319-1329 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2002. Vol. 16, no 10, 1319-1329 p.
Antigen presentation, Apoptosis, CD4 T cells, CD8 T cells, Dendritic cells, HIV-1, Immune response
IdentifiersURN: urn:nbn:se:liu:diva-46953DOI: 10.1097/00002030-200207050-00003OAI: oai:DiVA.org:liu-46953DiVA: diva2:267849