Induction of Fas Ligand-Mediated Apoptosis by Interferon-α

Kirou, Kyriakos A.; Krishna, Radha; Maria, Vakkalanka; Butler, Jerry F.; Crow, Mary K.

doi:10.1006/clim.2000.4866

Cited by 58 publications

(33 citation statements)

References 52 publications

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“…In contrast to the uptake of apoptotic cells by DCs, which results in the processing and presentation of Ag to T cells (1), the CD14-mediated uptake of apoptotic cells by macrophages diverts the phagocytosed antigenic material from T-cell recognition (17). This mechanism could be enhanced by the known effect of IFN-␣ on the CD95-mediated pathway of apoptosis: increased levels of expression of CD95 on infected cells (12,28,45) and the concomitant up-regulation of the Fas ligand on NK effector cells (20) may result in the accelerated apoptosis of infected cells, which in turn are removed by CD14-expressing Kupffer cells without further activation of the infiltrating lymphocytes. In line with this interpretation, we found no evidence of a significant involvement of DCs in the liver.…”

Section: Discussionmentioning

confidence: 99%

Antiviral Treatment with Alpha Interferon Up-Regulates CD14 on Liver Macrophages and Its Soluble Form in Patients with Chronic Hepatitis B

Carotenuto

Riel

Artsen

et al. 2005

Antimicrob Agents Chemother

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To investigate whether therapy with alpha interferon (IFN-␣) induces changes in intrahepatic antigenpresenting cells (APCs), we obtained liver biopsy specimens before, during, and after therapy with IFN-␣ from chronic hepatitis B patients whose viral load had already been reduced by at least 8 weeks of treatment with lamivudine. HLA-DR, CD1a, and CD83 were not modified by the therapy. The intralobular expression of CD68 on Kupffer cells remained stable, denoting no changes in the number of resident macrophages during IFN-␣ treatment. In contrast, CD14 was weakly expressed in the absence of IFN-␣ and was significantly up-regulated during therapy. At the same time, the levels of soluble CD14 and interleukin-10 in plasma increased significantly. In vitro, monocytes maintained in the presence of IFN-␣ differentiated into macrophages or dendritic cells with higher levels of expression of CD14 than that for the control cultures. During therapy with IFN-␣, T-cell infiltration in the portal spaces was reduced, mainly due to a significant decrease in the number of CD8 ؉ T cells. These findings show that IFN-␣ is biologically active on APCs in vivo and in vitro and suggest that this newly described regulatory function, together with the already known inhibitory effects on lymphocytes, may cooperate to reduce inflammation and consequent tissue damage in patients with chronic viral hepatitis.

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Section: Discussionmentioning

confidence: 99%

Antiviral Treatment with Alpha Interferon Up-Regulates CD14 on Liver Macrophages and Its Soluble Form in Patients with Chronic Hepatitis B

Carotenuto

Riel

Artsen

et al. 2005

Antimicrob Agents Chemother

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“…Exposure to ultraviolet light or infections will generate more apoptotic or necrotic material, and the resulting inflammatory process will promote the extracellular release of nucleic acid (95). In addition, IFN␣ can increase both apoptosis (96) and expression of autoantigens (85), thereby adding fuel to the autoimmune process.…”

Section: The Type I Ifn System In the Etiopathogenesis Of Slementioning

confidence: 99%

The type I interferon system in systemic lupus erythematosus

Rönnblom

Eloranta

Alm

2006

Arthritis & Rheumatism

304

246

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“…For cell cycle analysis, cells were washed, alcohol fixed, stained with 50 g/ml propidium iodide (PI), and analyzed using a FACScan (BD Biosciences, San Diego, CA) flow cytometer for DNA content, as previously described (29). The percentage of mononuclear cells containing subdiploid DNA reflects the proportion of apoptotic cells.…”

Section: Determination Of Apoptosismentioning

confidence: 99%

T Cell Proliferation Induced by Autologous Non-T Cells Is a Response to Apoptotic Cells Processed by Dendritic Cells

Chernysheva

Kirou

Crow

2002

The Journal of Immunology

Self Cite

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Self-reactive T cells are present in the mature immune repertoire as demonstrated by T cell proliferation induced by autologous non-T cells in the autologous mixed lymphocyte reaction. This reaction generates regulatory T cells in vitro and may reflect immune regulatory pathways in vivo, but the antigenic peptides recognized remain uncharacterized. We revisited this issue in light of the importance of apoptosis in immune regulation. We found that apoptosis among peripheral blood non-T stimulator cells is associated with augmented induction of autologous T cell proliferation. Our data show that caspase activity in the non-T stimulator population is essential for induction of autologous T cell proliferation, suggesting that cellular components in the non-T cell fraction are enzymatically modified, most likely by effector caspases, and have a direct or indirect effect on autoreactive T cell activation. Furthermore, exposure of macrophage-derived dendritic cells to apoptotic non-T cells augments autologous T cell proliferation, and blockade of αvβ5 integrin, but not αvβ3, inhibits the capacity of irradiated non-T cells or dendritic cells to stimulate autologous T cell proliferation. These experiments, using an entirely autologous system, suggest the interpretation that autoreactive T cells may recognize self-Ags modified through the actions of caspases and presented to T cells by dendritic cells. Induction of an in vivo autologous mixed lymphocyte reaction by caspase-modified self-Ags present in apoptotic cells may represent a mechanism to maintain peripheral immune tolerance.

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Induction of Fas Ligand-Mediated Apoptosis by Interferon-α

Cited by 58 publications

References 52 publications

Antiviral Treatment with Alpha Interferon Up-Regulates CD14 on Liver Macrophages and Its Soluble Form in Patients with Chronic Hepatitis B

Antiviral Treatment with Alpha Interferon Up-Regulates CD14 on Liver Macrophages and Its Soluble Form in Patients with Chronic Hepatitis B

The type I interferon system in systemic lupus erythematosus

T Cell Proliferation Induced by Autologous Non-T Cells Is a Response to Apoptotic Cells Processed by Dendritic Cells

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