Home LiteratureArticle Details
PMID: 11572934 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: a CD4+ T cell regulatory mechanism.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 21 ·2001-10-09 ·Pages 12150-5

Lila N, Rouas-Freiss N, Dausset J, Carpentier A, Carosella ED

Abstract

We recently reported that the nonclassical HLA class I molecule HLA-G was expressed in the endomyocardial biopsies and sera of 16% of heart transplant patients studied. The aim of the present report is to identify cells that may be responsible for HLA-G protein expression during the allogeneic reaction. Carrying out mixed lymphocyte cultures in which the responder cell population was depleted either in CD4(+) or CD8(+) T cells, we found that soluble HLA-G5 protein but not the membrane-bound HLA-G isoform was secreted by allo-specific CD4(+) T cells from the responder population, which suppressed the allogeneic proliferative T cell response. This inhibition may be reversed by adding the anti-HLA-G 87G antibody to a mixed lymphocyte culture. That may indicate a previously uncharacterized regulatory mechanism of CD4(+) T cell proliferative response.

MeSH Terms
Apoptosis/immunology Blotting, Western/methods CD4-Positive T-Lymphocytes/immunology,metabolism Cell Division Flow Cytometry/methods HLA Antigens/biosynthesis,immunology HLA-G Antigens Histocompatibility Antigens Class I/biosynthesis,immunology Humans Immunoenzyme Techniques Isoantigens/biosynthesis,immunology Lymphocyte Culture Test, Mixed Protein Isoforms/biosynthesis,immunology Solubility Subcellular Fractions
Chemicals
HLA Antigens HLA-G Antigens Histocompatibility Antigens Class I Isoantigens Protein Isoforms
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lila N
Service de Recherches en Hémato-Immunologie, Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, Départment de Recherche Médicale, Hôpital Saint-Louis, 1 Avenue Claude-Vellefaux, 75010 Paris, France.
Rouas-Freiss N
Dausset J
Carpentier A
Carosella E D
References (36)
36 references, click to expand
  1. A specific interferon (IFN)-stimulated response element of the distal HLA-G promoter binds IFN-regulatory factor 1 and mediates enhancement of this nonclassical class I gene by IFN-beta.
    J Biol Chem. 2001 Mar 2;276(9):6133-9 PMID: 11087747
  2. A soluble form of the HLA-G antigen is encoded by a messenger ribonucleic acid containing intron 4.
    J Immunol. 1994 Dec 15;153(12):5516-24 PMID: 7989753
  3. Implication of HLA-G molecule in heart-graft acceptance.
    Lancet. 2000 Jun 17;355(9221):2138 PMID: 10902633
  4. HLA-G has a concentration-dependent effect on the generation of an allo-CTL response.
    Immunology. 2000 Oct;101(2):191-200 PMID: 11012772
  5. A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells.
    J Exp Med. 1997 Dec 1;186(11):1809-18 PMID: 9382880
  6. Regulation of the human allogenic proliferative response in vitro. II. Production of soluble suppressor factors by suppressor T cells and evidence in favor of "acceptor" cells for suppression among unprimed lymphocytes.
    Immunogenetics. 1981;14(1-2):117-27 PMID: 6459996
  7. Modulation of HLA-G expression in human thymic and amniotic epithelial cells.
    Hum Immunol. 2000 Nov;61(11):1095-101 PMID: 11137212
  8. Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8.
    J Immunol. 2000 Jun 15;164(12):6100-4 PMID: 10843658
  9. HLA-G class I gene expression in normal and malignant hematopoietic cells.
    Hum Immunol. 1998 Aug;59(8):524-8 PMID: 9712358
  10. HLA-G suppresses proliferation of CD4(+) T-lymphocytes.
    J Reprod Immunol. 2000 Aug;48(1):17-26 PMID: 10996380
  11. Allosensitized T cells produce soluble factors susceptible to suppress allogeneic proliferation but not to interfere on cell mediated cytotoxicity.
    Medicina (B Aires). 1981;41 Suppl:65-76 PMID: 6212736
  12. Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies.
    Cancer Res. 1999 Apr 15;59(8):1954-60 PMID: 10213506
  13. IL-10 selectively induces HLA-G expression in human trophoblasts and monocytes.
    Int Immunol. 1999 May;11(5):803-11 PMID: 10330285
  14. A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules.
    Immunity. 1997 Aug;7(2):273-82 PMID: 9285411
  15. Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture.
    Mol Hum Reprod. 2001 Feb;7(2):195-200 PMID: 11160846
  16. HLA-G2, -G3, and -G4 isoforms expressed as nonmature cell surface glycoproteins inhibit NK and antigen-specific CTL cytolysis.
    J Immunol. 2001 Apr 15;166(8):5018-26 PMID: 11290782
  17. Inhibitory receptors sensing HLA-G1 molecules in pregnancy: decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor.
    Proc Natl Acad Sci U S A. 1999 May 11;96(10):5674-9 PMID: 10318943
  18. Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11520-5 PMID: 9326642
  19. A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells.
    J Exp Med. 1999 Apr 5;189(7):1093-100 PMID: 10190900
  20. Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules.
    J Immunol. 1998 Apr 1;160(7):3096-100 PMID: 9531263
  21. Association of soluble HLA-G plasma levels with HLA-G alleles.
    Tissue Antigens. 2001 Jan;57(1):15-21 PMID: 11169254
  22. HLA-G and HLA-E: fundamental and Pathophysiological aspects.
    Immunol Today. 2000 Nov;21(11):532-4 PMID: 11186460
  23. Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts.
    J Exp Med. 1997 Jul 21;186(2):289-98 PMID: 9221758
  24. Identification of HLA-G7 as a new splice variant of the HLA-G mRNA and expression of soluble HLA-G5, -G6, and -G7 transcripts in human transfected cells.
    Hum Immunol. 2000 Nov;61(11):1138-49 PMID: 11137219
  25. HLA-G inhibits the allogeneic proliferative response.
    J Reprod Immunol. 1999 Jul;43(2):203-11 PMID: 10479056
  26. A soluble HLA-G protein that inhibits natural killer cell-mediated cytotoxicity.
    Transplant Proc. 2001 May;33(3):2355-9 PMID: 11377558
  27. Expression of HLA-G in human mononuclear phagocytes and selective induction by IFN-gamma.
    J Immunol. 1996 Jun 1;156(11):4224-31 PMID: 8666791
  28. Human leukocyte antigen-G-expressing cells differently modulate the release of cytokines from mononuclear cells present in the decidua versus peripheral blood.
    Am J Reprod Immunol. 2001 Feb;45(2):94-9 PMID: 11216880
  29. Soluble HLA-G circulates in maternal blood during pregnancy.
    Am J Obstet Gynecol. 2000 Sep;183(3):682-8 PMID: 10992193
  30. Expression analysis of classic and non-classic HLA molecules before interferon alfa-2b treatment of melanoma.
    Lancet. 2000 Jul 15;356(9225):220-1 PMID: 10963203
  31. A class I antigen, HLA-G, expressed in human trophoblasts.
    Science. 1990 Apr 13;248(4952):220-3 PMID: 2326636
  32. Soluble HLA-G in human placentas: synthesis in trophoblasts and interferon-gamma-activated macrophages but not placental fibroblasts.
    Hum Immunol. 1998 Jul;59(7):435-42 PMID: 9684993
  33. Human placental HLA-G expression is restricted to differentiated cytotrophoblasts.
    J Immunol. 1995 Apr 15;154(8):3771-8 PMID: 7706718
  34. Modulation of HLA-G antigens expression in myelomonocytic cells.
    Hum Immunol. 2000 Nov;61(11):1086-94 PMID: 11137211
  35. Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens.
    Proc Natl Acad Sci U S A. 1992 May 1;89(9):3947-51 PMID: 1570318
  36. HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance.
    Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4510-5 PMID: 9539768
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.201407398
Published
2001-10-09
Epub
2001-00-25
Pages
12150-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC59783
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.201407398 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2