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.
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.
Authors: Letícia de Aquino Penteado; Naiara Naiana Dejani; Felipe Fortino Verdan; Allan Botinhon Orlando; Victoria Eugenia Niño; Fernanda De Nuzzi Dias; Ana Carolina Guerta Salina; Alexandra Ivo Medeiros Journal: Immunology Date: 2017-04-10 Impact factor: 7.397
Authors: I Frank; H Stössel; A Gettie; S G Turville; J W Bess; J D Lifson; I Sivin; N Romani; M Robbiani Journal: J Virol Date: 2008-03-26 Impact factor: 5.103
Authors: Concepción Marañón; Jean-François Desoutter; Guillaume Hoeffel; William Cohen; Daniel Hanau; Anne Hosmalin Journal: Proc Natl Acad Sci U S A Date: 2004-04-12 Impact factor: 11.205