Inducible Nonlymphoid Expression of Fas Ligand Is Responsible for Superantigen-Induced Peripheral Deletion of T Cells

Bonfoco, Emanuela; Stuart, Patrick M.; Brunner, Thomas; Lin, Tiejun; Griffith, Thomas S.; Yuan-fu, Gao; Nakajima, Hiroo; Henkart, Pierre A.; Ferguson, T.; Green, Douglas R.

doi:10.1016/s1074-7613(00)80668-8

Cited by 144 publications

(121 citation statements)

References 42 publications

(8 reference statements)

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“…It will be of interest to identify the non-T lineage cells that express FasL to kill 2C T cells when MHC class I is absent. Such a scenario has been reported previously for superantigen-induced T cell death, which appeared to depend upon FasL expression by non-hematopoietic cells [19]. Interestingly, in class I + recipient mice, we observed that increased numbers of both 2C/lpr and 2C/gld T cells were recovered compared to WT 2C cells.…”

Section: Discussionsupporting

confidence: 88%

Death of peripheral CD8⁺ T cells in the absence of MHC class I is Fas‐dependent and not blocked by Bcl‐x_L

2003

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Productive immune responses require an appropriate environment to support peripheral CD8 + T cell survival. Although host MHC class I molecules appear to be required for this process, the cellular and molecular requirements have not been comprehensively studied. Using adoptive transfer of 2C/recombinase-activating gene-2 (RAG-2) -/-TCR-transgenic T cells, we found that the survival of both naive and effector CD8 + T cells was dependent upon host expression of the same MHC class I alleles that supported thymic selection. Expression of appropriate MHC class I by either bone marrow-or non-bone-marrow-derived cells was sufficient, suggesting that professional antigen-presenting cells were not mandatory. In contrast to MHC class I, neither T cell expression of CD28 nor host expression of ICAM-1 was required for peripheral T cell survival. Finally, T cell death in the absence of appropriate host MHC class I was overcome by elimination of Fas signaling but not by overexpression of Bcl-x L by CD8 + T cells. These results suggest that, in the absence of a survival signal provided by engagement of host MHC/self peptide complexes, CD8 + T cells die via a Fas-dependent, mitochondria-independent pathway.

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Section: Discussionsupporting

confidence: 88%

Death of peripheral CD8⁺ T cells in the absence of MHC class I is Fas‐dependent and not blocked by Bcl‐x_L

2003

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“…Bonfoco et al (42) reported that i.v. administration of SEB induced a marked up-regulation of FasL in IHL, which, in turn, killed activated lymphocytes, leading to peripheral T cell deletion.…”

Section: Discussionmentioning

confidence: 99%

Administration of an Antigen at a High Dose Generates Regulatory CD4+ T Cells Expressing CD95 Ligand and Secreting IL-4 in the Liver

Watanabe

Yoshida

Shirai

et al. 2002

The Journal of Immunology

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Ags administered orally at a high dose are absorbed in immunogenic forms and perfuse the liver, which raises a question regarding the relevance of hepatic lymphocyte activation to the systemic hyporesponsiveness against the ingested Ag. Oral administration of 100 mg of OVA to the mice led to massive cell death of OVA-specific (KJ1-26+) CD4+ T cells by Fas-Fas ligand (FasL)-mediated apoptosis in the liver, which was associated with the emergence of hepatic KJ1-26+CD4+ T cells expressing FasL. Hepatic CD4+ T cells in OVA-fed mice secreted large amounts of IL-4, IL-10, and TGF-β1 upon restimulation in vitro and inhibited T cell proliferation. Adoptive transfer of these hepatic CD4+ T cells to naive mice and subsequent antigenic challenge led to suppression of T cell proliferation as well as IgG Ab responses to OVA; this effect was mostly abrogated by a blocking Ab to FasL. i.p. administration of an Ag at a high dose also generated hepatic CD4+FasL+ T cells with similar cytokine profile as T cells activated by oral administration of Ags at a high dose. Finally, we did not see an increase in FasL+ cells in the hepatic CD4+Vβ8+ T cell subset of MRL/lpr/lpr mice given staphylococcal enterotoxin B, indicating the requirement for Fas-mediated signals. These hepatic CD4+FasL+ regulatory cells may explain the tolerogenic property of the liver and play roles in systemic hyporesponsiveness induced by an Ag administered at a high dose.

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“…Therefore, the first model of AICD suggested that up-regulation of CD95L on activated T cells leads to either suicide or fratricide. However, an alternative hypothesis explained AICD in vivo based on the fact that non-lymphoid tissue responds to lymphocyte infiltration and TNF-a stimulation with up-regulation of CD95L [65,66]. This mechanism is thought to keep the destructive force of the immune system in check by inducing a localized temporary immunologically privileged state.…”

Section: Apoptosis In the Immune System Central Tolerance -Education mentioning

confidence: 99%

How apoptosis got the immune system in shape

Feig

Marynen

2007

Eur. J. Immunol.

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Inducible Nonlymphoid Expression of Fas Ligand Is Responsible for Superantigen-Induced Peripheral Deletion of T Cells

Cited by 144 publications

References 42 publications

Death of peripheral CD8⁺ T cells in the absence of MHC class I is Fas‐dependent and not blocked by Bcl‐x_L

Death of peripheral CD8⁺ T cells in the absence of MHC class I is Fas‐dependent and not blocked by Bcl‐x_L

Administration of an Antigen at a High Dose Generates Regulatory CD4+ T Cells Expressing CD95 Ligand and Secreting IL-4 in the Liver

How apoptosis got the immune system in shape

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Inducible Nonlymphoid Expression of Fas Ligand Is Responsible for Superantigen-Induced Peripheral Deletion of T Cells

Cited by 144 publications

References 42 publications

Death of peripheral CD8+ T cells in the absence of MHC class I is Fas‐dependent and not blocked by Bcl‐xL

Death of peripheral CD8+ T cells in the absence of MHC class I is Fas‐dependent and not blocked by Bcl‐xL

Administration of an Antigen at a High Dose Generates Regulatory CD4+ T Cells Expressing CD95 Ligand and Secreting IL-4 in the Liver

How apoptosis got the immune system in shape

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Death of peripheral CD8⁺ T cells in the absence of MHC class I is Fas‐dependent and not blocked by Bcl‐x_L

Death of peripheral CD8⁺ T cells in the absence of MHC class I is Fas‐dependent and not blocked by Bcl‐x_L