Extracellular matrix interacts with soluble CD95L: Retention and enhancement of cytotoxicity

Aoki, Kazunori; Kurooka, Masayuki; Chen, Jianjun; Petryniak, Jerzy; Nabel, Elizabeth G.; Nabel, Gary J.

doi:10.1038/86336

Cited by 89 publications

(67 citation statements)

References 31 publications

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“…In fact, a differential requirement of ligand oligomerization for the activation of distinct signaling pathways stimulated by the same TNF receptor type was recently observed by us in the TWEAKFn14 system (54). On the other hand, soluble CD95L can be secondarily activated naturally by binding to the extracellular matrix or aggregation due to an oxidative microenvironment (14,15), and it is thus not fully ruled out that such or related mechanisms play a role in the studies discussed above.…”

Section: Discussionmentioning

confidence: 99%

“…Worth mentioning, both of these possibilities could reflect physiologically relevant situations. In the bronchoalveolar lavage fluid derived from patients with lung injury, highly active aggregates of soluble CD95L are formed secondarily by oxidation (14), and binding of soluble CD95L to fibronectin potentiates its cytotoxic activity (15). Thus, the formation of CD95 signaling complexes and activation of intracellular signaling pathways are not a simple straightforward result of CD95L binding.…”

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confidence: 99%

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Signaling Active CD95 Receptor Molecules Trigger Co-translocation of Inactive CD95 Molecules into Lipid Rafts

Lang

Fick

Schäfer

et al. 2012

Journal of Biological Chemistry

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Background: Mechanisms of activation of the prototypical death receptor CD95 have been described. Results: Highly active CD95L variants (Fc-CD95L, membrane CD95L) stimulate the association of unliganded CD40-CD95 chimeras or of inactive complexes of CD95L trimers and CD95 with the lipid raft compartment. Conclusion: CD95 signaling triggers association of active and inactive CD95 species with lipid rafts. Significance: Identification of inactive CD95 species as targets of their active counterparts is described.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Signaling Active CD95 Receptor Molecules Trigger Co-translocation of Inactive CD95 Molecules into Lipid Rafts

Lang

Fick

Schäfer

et al. 2012

Journal of Biological Chemistry

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“…17 While membrane-bound CD95L efficiently mediates apoptosis in CD95 expressing cells by formation of trimers or higher molecular structures, s-CD95L can have pro-or antiapoptotic functions depending on the microenvironment. 17,18 s-CD95L is proapoptotic if oligomers are formed with the extracellular matrix but antiapoptotic by competing with the m-CD95L for binding to CD95 in the absence of oligomer formation. 18 Cells transfected with m-CD95L have been shown to efficiently induce cell death in T cell lines and lymphocytes.…”

mentioning

confidence: 99%

“…17,18 s-CD95L is proapoptotic if oligomers are formed with the extracellular matrix but antiapoptotic by competing with the m-CD95L for binding to CD95 in the absence of oligomer formation. 18 Cells transfected with m-CD95L have been shown to efficiently induce cell death in T cell lines and lymphocytes. 19,20 Thus, m-CD95L-expressing APC might be used in vitro to selectively deplete antigen-specific T cells in solid organ transplantations to prevent graft rejection or to remove host-reactive T cells from allogeneic bone marrow transplants to minimize the risk of graft-versus-host disease.…”

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confidence: 99%

Membrane-bound CD95 ligand expressed on human antigen-presenting cells prevents alloantigen-specific T cell response without impairment of viral and third-party T cell immunity

et al. 2006

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Genetically modified antigen-presenting cells (APC) represent an attractive strategy for in vitro immunomodulation. In the human system, APC expressing HLA-A1 and a membrane-bound form of CD95L (m-CD95L) were used for selective depletion of HLA-A1-specific T cells. In short-term assays, m-CD95L-expressing APC-induced apoptosis in activated T cells and the constitutive presence of m-CD95L and HLA-A1 expressing APC in long-term T cell cultures prevented the expansion of CD4 þ and CD8 þ HLA-A1-specifc T cells and the development of HLA-A1-specific cytotoxicity. However, immunity towards third party, viral and bacterial antigens was maintained and T cells spared from depletion could be induced to develop cytotoxicity towards unrelated antigens. Interestingly, inhibition of HLA-A1-specific T cell response absolutely requires the coexpression of m-CD95L and HLA-A1 antigen on the same APC. Thus, m-CD95L expressing APC might be used in clinical settings to obtain tolerance induction in allogeneic transplantation systems or autoimmune diseases. Apoptosis mediated by the CD95 system plays a pivotal regulatory role in the maintenance of immune homeostasis. Deficiency in CD95 or CD95L expression in T cells mediates lymphoproliferative disorders due to the lack of apoptosis induction. 1 Paradoxically, several molecules of the CD95 signaling pathway are also required for T cell activation and proliferation. 2 In addition to T cells, live and death of antigenpresenting cells, which initiate T cell responses has to be tightly controlled to avoid the establishment of autoimmunity. 3 Activation-induced cell death (AICD) represents an apoptosis mechanism mediated via the interaction of CD95 with its ligand CD95L, to mediate T cell death and initiate the termination of an immune response to maintain tolerance to self antigens and to prevent autoimmunity. 4 Owing to the constitutive expression of CD95L in immune privileged organs such as testis or eye, 5,6 CD95L was considered as an immunoprotective agent able to counterattack activated T cells in vivo. However, the role of CD95L in transplantation tolerance is still controversial. While allogeneic pancreatic islands transplanted together with syngeneic CD95L expressing myoblasts were tolerated, 7 allogeneic CD95L expressing pancreatic b cells were rejected due to increased neutrophil infiltration. 8 Lack of immunogenicity of tumors and resistance towards T cell attacks were also correlated with the expression of CD95L on tumor tissues. Such tumors were shown to kill CD95-positive cells in vitro. 9 However, transfection of CD95L into murine tumor cells did not enhance tumor growth, but instead induced accelerated tumor rejection by neutrophils in vivo. [10][11][12] Systemic immunomodulation by CD95L was successfully achieved by antigen-presenting cells modified to express CD95L. 13 In mice antigen-specific elimination of activated T cells by engagement of CD95L on APC and CD95 on the activated T cells has been demonstrated in several models. 14,15 This approach benefits from the hig...

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“…Since substantial numbers of CD4 ϩ and CD8 ϩ T cells are retained in nonlymphoid organs following immune responses (15,28), heparan sulfate-bound IL-2 may provide a survival factor for these cells. Finally, because soluble Fas ligand may also be bound by the extracellular matrix (29), colocalization of both IL-2 and Fas ligand by the extracellular matrix may represent a potent means to limit the number of memory T cells remaining in tissues following immune responses or to eliminate T cells inappropriately stimulated by self-Ag.…”

Section: And Ref 9)mentioning

confidence: 99%

Propagation and Control of T Cell Responses by Heparan Sulfate-Bound IL-2

Wrenshall

Platt

Stevens

et al. 2003

The Journal of Immunology

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IL-2, a cytokine produced by T cells, is a key regulator of immune responses and T cell homeostasis. Controlling the availability of IL-2 is consequently of significant import to the immune system. Like other cytokines, IL-2 is thought to function as a soluble agonist, transiently present when secreted in response to appropriate stimuli. In this study, we show that the most salient properties of IL-2, propagation and control of T cell responses, are mediated in vivo by bound and not free cytokine and specifically by heparan sulfate-bound IL-2. These findings necessitate a new look at how IL-2 regulates immune responses and support the notion that the microenvironment plays a determining role in modulating the character of immune responses.

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Extracellular matrix interacts with soluble CD95L: Retention and enhancement of cytotoxicity

Cited by 89 publications

References 31 publications

Signaling Active CD95 Receptor Molecules Trigger Co-translocation of Inactive CD95 Molecules into Lipid Rafts

Signaling Active CD95 Receptor Molecules Trigger Co-translocation of Inactive CD95 Molecules into Lipid Rafts

Membrane-bound CD95 ligand expressed on human antigen-presenting cells prevents alloantigen-specific T cell response without impairment of viral and third-party T cell immunity

Propagation and Control of T Cell Responses by Heparan Sulfate-Bound IL-2

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