Th1 CD4+ lymphocytes delete activated macrophages through the Fas/APO-1 antigen pathway.

Ashany, Dalit; Song, Xin; Lacy, Elizabeth; Nikolić‐Žugić, Janko; Friedman, Steven; Elkon, Keith B.

doi:10.1073/pnas.92.24.11225

Cited by 112 publications

(100 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The normal microbial flora of the intestine stimulates B and T lymphocytes as well as APCs in the peritoneal cavity (36 -38). The elevated IL-12 levels in B6/lpr mice may reflect an inability to delete activated peritoneal APCs, because normal macrophages activated by IFN-␥ or TNF-␣ up-regulate Fas expression and are eliminated by apoptosis (39,40). Consistent with that notion, the macrophage compartment expands in MRL/lpr mice (41).…”

Section: Spontaneous Il-12 Production In B6/lpr Micementioning

confidence: 75%

Fas and Fas Ligand Mutations Inhibit Autoantibody Production in Pristane-Induced Lupus

Satoh

Weintraub

Yoshida

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Mutations of Fas (lpr) or Fas ligand (gld) cause a limited lupus-like syndrome in B6 mice by interfering with the deletion of autoreactive B and/or T cells. A more generalized lupus syndrome reminiscent of that of MRL mice can be induced in nonautoimmune strains by pristane, which causes a nonspecific inflammatory response in the peritoneal cavity. We hypothesized that, as in MRL mice, the lpr and gld mutations might accelerate lupus in pristane-treated mice. Pristane-treated B6 mice developed anti-nRNP/Sm, Su, and ribosomal P Abs, but little anti-ssDNA or chromatin. In contrast, B6/lpr and B6/gld mice spontaneously developed anti-ssDNA/chromatin Abs, but not anti-nRNP/Sm/Su/ribosomal P. Unexpectedly, B6/lpr and B6/gld mice were highly resistant to the induction by pristane of IgM anti-ssDNA (2 wk) and IgG anti-nRNP/Sm/Su/ribosomal P autoantibodies (6 mo), suggesting that intact Fas signaling is necessary. Interestingly, pristane did not enhance IgG chromatin Ab production in B6/lpr or B6/gld mice, suggesting that it did not influence the production of autoantibodies that develop spontaneously in the setting of Fas deficiency. Pristane treatment also decreased lymphoproliferation in B6/lpr mice. Increased production of IL-12 was associated consistently with the production of anti-nRNP/Sm/Su/ribosomal P as well as anti-DNA/chromatin. In contrast, production of anti-DNA/chromatin Abs was associated with IL-6 overproduction in pristane-treated mice, but not in lpr mice. The data strongly support the idea that different subsets of autoantibodies are regulated differentially by cytokine stimulation and/or Fas signaling.

show abstract

Section: Spontaneous Il-12 Production In B6/lpr Micementioning

confidence: 75%

Fas and Fas Ligand Mutations Inhibit Autoantibody Production in Pristane-Induced Lupus

Satoh

Weintraub

Yoshida

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Histological findings suggest that these substances stimulate the migration of polymorphonuclear and mononuclear cells, and accelerate connective tissue regeneration and angiogenesis [1,12].…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Macrophage Activation by Chitin Derivatives

Mori

Murakami

Okumura

et al. 2005

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. In order to analyze the detailed mechanisms responsible for macrophage activation by chitin derivatives, resident peritoneal macrophages were prepared and stimulated with chitin, chitosan and low-molecular weight chitosan. Our findings were as follows: (i) chitosan induced apoptosis of peritoneal macrophages, but this did not occur when chitin or water soluble low-molecular weight chitosan were used; (ii) chitosan treatment induced activation markers, such as the major histocompatibility complex (MHC) class I, class II, Fc receptors, transferrin receptor, mannose receptor, Fas, and macrophage inflammatory protein (MIP)-2, whereas chitin and low molecular weight soluble chitosan induced only the expression of MHC class I and II molecules; (iii) apoptosis induced by chitosan was mediated by the Fas signaling pathway, in response to phagocytosis via the mannose receptor. We conclude that since chitosan activates macrophages, this may be the mechanism by which it accelerates wound healing.

show abstract

“…Both CD4 + and CD8 + T-cell-mediated killing of cognate APC populations including DCs, B cells, and macrophages has been reported in several studies [20][21][22][23][43][44][45] and was shown to be mediated via Fas ligand (FasL)-dependent 20,[46][47][48] or -independent mechanisms. 23,44 Similarly, CD8 + CTL-mediated elimination of transplanted neo-antigen-positive T cells and other hematopoietic cells has been previously demonstrated in vivo both in animal models [27][28][29] and humans.…”

Section: Immune Responses To Gene-modified Dendritic Cells N Chinnasamentioning

confidence: 99%

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

et al. 2005

View full text Add to dashboard Cite

Genetically modified dendritic cell (DC) vaccines expressing tumor-associated antigens are currently used for cancer immunotherapy. Peripheral blood (PB) monocyte precursors are a relatively convenient source of DCs for use in clinical studies, but are often contaminated by lymphocytes. The current study was conducted to examine the impact of Tlymphocyte contamination on genetically modified DC product. PB monocyte-derived DCs were efficiently transduced (75-95%) with an HIV-1-based self-inactivating lentiviral vector encoding a model antigen, the enhanced green fluorescent protein (eGFP). The lymphocyte-free DC culture transduced with Lenti-eGFP showed stable expression of eGFP without measurable decline in viability. In contrast, the eGFP-positive DCs disappeared rapidly in transduced DC cultures containing lymphocyte contaminants, concurrent with detectable activation and expansion of T-lymphocytes. Upon antigen recall, these T cells elicited major histocompatability complex-restricted antigen-specific cytotoxicity against eGFP-positive autologous DCs and mitogen-stimulated T lymphoblasts, mainly through the perforin-mediated pathway. In summary, this study demonstrate that the relative purity of DC cultures could determine the persistence of gene-modified DC, which may affect the induction of effective immune responses by DC vaccination strategies. Gene Therapy (2005) 12, 259-271.

show abstract

Th1 CD4+ lymphocytes delete activated macrophages through the Fas/APO-1 antigen pathway.

Abstract: The Fas/APO-1 cytotoxic pathway plays an important role in the regulation of peripheral immunity. Recent

Cited by 112 publications

References 45 publications

Fas and Fas Ligand Mutations Inhibit Autoantibody Production in Pristane-Induced Lupus

Fas and Fas Ligand Mutations Inhibit Autoantibody Production in Pristane-Induced Lupus

Mechanism of Macrophage Activation by Chitin Derivatives

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

Contact Info

Product

Resources

About