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- Larsson, M., et al.
(författare)
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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
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Ingår i: AIDS. - : Ovid Technologies (Wolters Kluwer Health). - 0269-9370 .- 1473-5571. ; 16:10, s. 1319-1329
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Eklund, Lena K., et al.
(författare)
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Abnormal expression of proteins in Notch and Wnt pathways in human squamous cell carcinoma of the skin
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background Members of the Notch pathway are involved in various differentiation processes. Signalling via the Wnt/ß-catenin-pathway controls transcription of genes involved in proliferation events. These two pathways are interconnected through the cytoplasmic protein Dishevelled (Dvl-1).Objectives To evaluate the expression patterns of Notch1, Dvl-1 and ß-catenin proteins in human squamous cell carcinomas of the skin.Methods 40 formalin-fixed paraffin-embedded SCCs were included in this study. Expression was detected with immunohistochemistry using avidin-biotin and DAB visualization.Results The majority of the normal epidermal cells lacked expression of Notch1, while the dysplastic and invasive tumour cells showed strong staining. Expression of Dvl-1 was observed in normal human epidermis, with a more intense staining indysplastic cells in 8 of 38 (21%) cases. Besides the expected cytoplasmic staining, 27 of 38 (71%) secs displayed nuclear staining and a potential nuclear localisation signal was identified. ß-catenin showed membranous and weak cytoplasmic staining in normal as well as tumour cells.Conclusions We have found enhanced expression of Notch1 in the majority of SCCs, indicating a disturbed differentiation process. We have also for the first time showed over-expression of Dvl-1 in dysplastic epidermal cells as well as normal staining of the nucleus. A classical nuclear localization signal is also identified in the Dvl-1 isoform A, whereas two other isoforms lack this recognition sequence.
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