Cutting Edge: Soluble HLA-G1 Triggers CD95/CD95 Ligand-Mediated Apoptosis in Activated CD8+ Cells by Interacting with CD8

Fournel, Sylvie; Aguerre-Girr, Maryse; Huc, Xavier; Lenfant, Françoise; Alam, Antoine; Toubert, Antoine; Bensussan, Armand; Bouteiller, Philippe Le

doi:10.4049/jimmunol.164.12.6100

Cited by 424 publications

(303 citation statements)

References 29 publications

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“…In particular, soluble HLA-G induces apoptosis of CD8 + T and NK cells and may participate in allograft tolerance through peripheral deletion of alloreactive T cells after allotransplantation in vivo [21,22]. Previous analysis of the functional role of both HLA-G1 and HLA-G5 in mixed lymphocyte reaction showed that both suppress the alloproliferative response of T cells [23,24,29].…”

Section: Discussionmentioning

confidence: 99%

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Alloreactive CD4⁺ and CD8⁺ T cells express the immunotolerant HLA‐G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients

et al. 2004

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HLA‐G displays immunotolerogenic properties towards the main effector cells involved in graft rejection through inhibition of NK‐ and CTL‐mediated cytolysis and CD4+ T cell alloproliferation. HLA‐G expression is restricted in healthy tissues to trophoblast and thymus but is extended to various tissues under pathological conditions. HLA‐G was detected in allograft biopsies and sera from transplanted patients who displayed a better graft acceptance. However, the cells involved in such de novo expression of HLA‐G remain to be characterized. By flow cytometry and confocal microscopy, we demonstrated that, following allogeneic stimulation in vitro, both CD4+ and CD8+ T cell subsets can express membrane‐bound HLA‐G1 and/or soluble HLA‐G5molecules. Such HLA‐G1/‐G5 expression is regulated at the transcriptional level. Soluble HLA‐G5 could be detected by using a novel monoclonal antibody, 5A6G7, specific for the intron 4‐retaining sequence of HLA‐G5. Finally, the biological relevance of these data was provided by analysis of transplanted patients in whom we identified both CD4+ and CD8+ T cells expressing HLA‐G. The HLA‐G‐positive T cells we describe here may constitute a cellular source of HLA‐G after allotransplantation and may be involved in the improved graft acceptance which is observed in HLA‐G‐positive transplanted patients.

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Section: Discussionmentioning

confidence: 99%

“…HLA-G leader peptide stabilizes the cell-surface expression of another non-classical HLA class I inhibitory molecule, HLA-E [20]. Finally, soluble HLA-G induces apoptosis of CD8 + T and NK cells through ligation with CD8, and via a Fas/FasLdependent mechanism [11,21,22].…”

Section: Introductionmentioning

confidence: 99%

Alloreactive CD4⁺ and CD8⁺ T cells express the immunotolerant HLA‐G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients

et al. 2004

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“…A role in controlling T cell expansion, blocking CTL activity, and inducing apoptosis in alloreactive T cells has been suggested for soluble HLA-G (19,20,44). Alternatively, soluble Mamu-AG might also help prevent antisperm immune responses following minor breaks in the bloodtestis barrier of the seminiferous basement membrane.…”

Section: Discussionmentioning

confidence: 99%

“…Unexpectedly, soluble HLA-G was detected not only in pregnancy, but also in nonpregnant women as well as males. Recent studies suggested that HLA-G5, one isoform of soluble HLA-G, can induce apoptosis in peripheral CD8 ϩ T cells via a Fas-Fas ligand mechanism (19), can suppress an allogeneic proliferative T cell response in mixed lymphocyte cultures (20), and can inhibit peripheral blood NK cell-mediated cytotoxicity (21). These results collectively suggest that while membrane-bound HLA-G may interact with resident leukocytes within the decidua, soluble HLA-G may act on blood cells in the peripheral circulation in both pregnant and nonpregnant individuals.…”

Section: T He Nonclassical Mhc Class I Molecule Hla-g Has Beenmentioning

confidence: 99%

A Soluble Isoform of the Rhesus Monkey Nonclassical MHC Class I Molecule Mamu-AG Is Expressed in the Placenta and the Testis

Ryan¹,

Grendell²,

Geraghty

et al. 2002

The Journal of Immunology

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The nonclassical MHC class I locus HLA-G is expressed primarily in the placenta, although other sites of expression have been noted in normal and pathological situations. In addition, soluble HLA-G isoforms have been detected in the serum of pregnant and nonpregnant women as well as men. The rhesus monkey placenta expresses a novel nonclassical MHC class I molecule Mamu-AG, which has features remarkably similar to those of HLA-G. We determined that the rhesus placenta expresses Mamu-AG mRNA (Mamu-AG5), retaining intron 4 as previously noted in HLA-G5. Immunostaining experiments with Ab 16G1 against the soluble HLA-G5 intron 4 peptide demonstrated that an immunoreactive protein(s) was present in the syncytiotrophoblasts of the chorionic villi of the rhesus placenta, within villous cytotrophoblasts, and occasionally within cells of the villous stroma. The Mamu-AG5 mRNA was readily detected in rhesus testis (although not in ejaculated sperm). Whereas an Ab against membrane-bound Mamu-AG stained few cells, primarily in the interstitium of the testis, there was consistent immunostaining for Mamu-AG5 in cells within the seminiferous tubules, which was corroborated by localization of Mamu-AG mRNA by in situ hybridization. While primary spermatocytes were negative, Sertoli cells, spermatocytes, and spermatids were consistently positive for 16G1 immunostaining. The specific recognition of the soluble Mamu-AG isoform was confirmed by Western blotting of Mamu-AG5 expressed in heterologous cells. The results demonstrate that a soluble nonclassical MHC class I molecule is expressed in the rhesus monkey placenta and testis, and confirm and extend the unique homology between HLA-G and the rhesus nonclassical molecule Mamu-AG.

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“…Additional experiments have shown that fragments of amniotic membrane exert immunosuppressive properties in mixed lymphocyte reactions [30].…”

Section: Discussionmentioning

confidence: 99%

Amniotic stem cells repair ureteric defect: a study to evaluate the feasibility of amniotic membrane as a graft in surgical reconstruction

et al. 2009

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Cutting Edge: Soluble HLA-G1 Triggers CD95/CD95 Ligand-Mediated Apoptosis in Activated CD8+ Cells by Interacting with CD8

Cited by 424 publications

References 29 publications

Alloreactive CD4⁺ and CD8⁺ T cells express the immunotolerant HLA‐G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients

Alloreactive CD4⁺ and CD8⁺ T cells express the immunotolerant HLA‐G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients

A Soluble Isoform of the Rhesus Monkey Nonclassical MHC Class I Molecule Mamu-AG Is Expressed in the Placenta and the Testis

Amniotic stem cells repair ureteric defect: a study to evaluate the feasibility of amniotic membrane as a graft in surgical reconstruction

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Cutting Edge: Soluble HLA-G1 Triggers CD95/CD95 Ligand-Mediated Apoptosis in Activated CD8+ Cells by Interacting with CD8

Cited by 424 publications

References 29 publications

Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA‐G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients

Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA‐G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients

A Soluble Isoform of the Rhesus Monkey Nonclassical MHC Class I Molecule Mamu-AG Is Expressed in the Placenta and the Testis

Amniotic stem cells repair ureteric defect: a study to evaluate the feasibility of amniotic membrane as a graft in surgical reconstruction

Contact Info

Product

Resources

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Alloreactive CD4⁺ and CD8⁺ T cells express the immunotolerant HLA‐G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients

Alloreactive CD4⁺ and CD8⁺ T cells express the immunotolerant HLA‐G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients