Engagement of CD44 up-regulates Fas Ligand expression on T cells leading to activation-induced cell death

Nakano, Kazuhisa; Saito, Kazuyoshi; Mine, Shinichiro; Matsushita, Sho; Tanaka, Yoshiya

doi:10.1007/s10495-006-0488-8

Cited by 32 publications

(25 citation statements)

References 45 publications

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“…This may relate to the extent of HA binding in activated T cells, as CD44-dependent AICD induced with immobilized CD44 mAbs was dramatic in both cell types. CD44 cross-linking can increase surface expression of FasL in human peripheral blood T cells (29). However, the independence of these two pathways during AICD in mice was demonstrated using MRL/lpr T cells that lack functional Fas, but were still susceptible to CD44 and HAdependent AICD.…”

Section: Discussionmentioning

confidence: 99%

“…However, another study using CD44 and Fas double null mice reported a reduction in lymphoproliferative symptoms when compared with Fas null mice (27). In addition, studies with human Jurkat T lymphoma cells and peripheral blood T cells have indicated that CD44 has the potential to affect Fas-dependent cell death (28,29), and CD44 cross-linking can reduce apoptosis and AICD in T cell lines (30,31). Thus the precise role of CD44 in AICD is not clear and the effect of the interaction with its physiological ligand, HA, has not been determined.…”

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confidence: 99%

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Hyaluronan Induces Cell Death in Activated T Cells through CD44

Ruffell

Johnson

2008

The Journal of Immunology

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In the immune system, leukocyte activation induces CD44 to bind hyaluronan, a component of the extracellular matrix. Here we used gain and loss of hyaluronan-binding mutants of CD44 to examine the consequence of hyaluronan binding in T cells. Jurkat T cells transfected with CD44 mutated at S180, which prevented the addition of chondroitin sulfate, displayed constitutively high levels of hyaluronan binding. These cells were more susceptible to activation-induced cell death, whereas cells expressing a CD44 mutant unable to bind hyaluronan (R41A) were resistant to cell death. In TCR or PMA activated Jurkat T cells, hyaluronan induced rapid cell death. This depended on the level of hyaluronan binding by the cell, and the amount and size of hyaluronan. High molecular mass hyaluronan had the greatest effect and cell death occurred independently of Fas and caspase activation. In splenic T cells, high hyaluronan binding occurred in a subpopulation of cells undergoing activation-induced cell death. In addition, hyaluronan induced cell death in ∼10% of reactivated splenic T cells when Fas-dependent apoptosis was prevented by Ab blocking or in Fas negative MRL/lpr T cells. This demonstrates that hyaluronan can induce cell death in activated, high hyaluronan binding T cells via a Fas-independent mechanism.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Hyaluronan Induces Cell Death in Activated T Cells through CD44

Ruffell

Johnson

2008

The Journal of Immunology

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“…Thereby CD44 contributes to memory Th1 cell generation [77]. At the same time CD44 is able to promote AICD in T cells by at least two distinct mechanisms: (i) up-regulation of Fas ligand surface expression on peripheral T cells [78], (ii) Fas independent induction of apoptosis in activated T cells via HA [79].…”

Section: Physiological Function In Cells Of Hematopoietic Originmentioning

confidence: 99%

CD44 in hematological neoplasias

2011

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“…Further studies are required to characterize the CD8 ϩ T cells responsible for apoptosis induction and the specificity of this response. We hypothesize that CD8 ϩ T cells responsible for AM⌽ apoptosis highly express CD44, which regulates their migration to the alveolus and enhances their FasL expression (2,37).…”

Section: Discussionmentioning

confidence: 99%

Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation

Kearns

Barthel

Bednarek

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Janssen WJ. Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation. Am J Physiol Lung Cell Mol Physiol 307: L62-L70, 2014. First published May 16, 2014 doi:10.1152/ajplung.00273.2013.-Apoptosis of alveolar macrophages and their subsequent clearance by neighboring phagocytes are necessary steps in the resolution of acute pulmonary inflammation. We have recently identified that activation of the Fas death receptor on the cell surface of macrophages drives macrophage apoptosis. However, the source of the cognate ligand for Fas (FasL) responsible for induction of alveolar macrophage apoptosis is not defined. Given their known role in the resolution of inflammation and ability to induce macrophage apoptosis ex vivo, we hypothesized that T lymphocytes represented a critical source of FasL. To address this hypothesis, C57BL/6J and lymphocyte-deficient (Rag-1 Ϫ/Ϫ ) mice were exposed to intratracheal lipopolysaccharide to induce pulmonary inflammation. Furthermore, utilizing mice expressing nonfunctional FasL, we adoptively transferred donor lymphocytes into inflamed lymphocyte-deficient mice to characterize the effect of lymphocyte-derived FasL on alveolar macrophage apoptosis in the resolution of inflammation. Herein, evidence is presented that lymphocytes expressing FasL enhance alveolar macrophage apoptosis during the resolution of LPS-induced inflammation. Moreover, lymphocyte induction of alveolar macrophage apoptosis results in contraction of the alveolar macrophage pool, which occurs in a FasLdependent manner. Specifically, FasL-expressing CD8 ϩ T lymphocytes potently induce alveolar macrophage apoptosis and contraction of the alveolar macrophage pool. Together, these studies identify a novel role for CD8 ϩ T lymphocytes in the resolution of acute pulmonary inflammation. macrophage; resolution; alveolus; apoptosis; Fas ligand ACUTE INFLAMMATION IS CHARACTERIZED by recruitment of leukocytes, including neutrophils and mononuclear cells, to sites of injury or infection. For inflammation to resolve and the tissue to revert to its preinjured state, the recruited leukocytes must be cleared from the site. The processes that regulate the death and removal of neutrophils in the early resolution of inflammation are well described (14). However, the mechanisms that underlie the subsequent removal of macrophages in the resolution of inflammation have garnered less attention. We have recently identified that alveolar macrophages (AM⌽s) undergo apoptosis and local phagocytic clearance during the resolution of pulmonary inflammation and that this is required for the return of macrophage numbers to their preinflammatory levels (23).We have further demonstrated that AM⌽ apoptosis occurs via the extrinsic apoptotic pathway and proceeds through activation of the TNF-related death receptor Fas (CD95) on the macrophage cell surface (23). However, the cellular source of the cognate ligand for Fas (FasL) is unknown (12). The primary goal of the current study was to det...

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Engagement of CD44 up-regulates Fas Ligand expression on T cells leading to activation-induced cell death

Cited by 32 publications

References 45 publications

Hyaluronan Induces Cell Death in Activated T Cells through CD44

Hyaluronan Induces Cell Death in Activated T Cells through CD44

CD44 in hematological neoplasias

Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation

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