HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune inhibitory receptor

Liang, Sai; Baibakov, Boris; Horuzsko, Anatolij

doi:10.1002/1521-4141(200209)32:9<2418::aid-immu2418>3.0.co;2-l

Cited by 128 publications

(96 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These data suggest that the reduction in HLA-G-specific CTLs is probably not specific for the pp65 response but is due to inhibitory triggering signals on the induction of antiviral CTL responses in transgenic mice. Further analysis showed that HLA-G modifies the function of murine DCs via interactions with the PIR-B inhibitory receptor, a homologue of the human inhibitory receptor ILT4 (Liang et al, 2002). This is consistent with results obtained in humans, where specific binding of HLA-G tetramers was associated with ILT4 on myelomonocytic cells (Allan et al, 1999).…”

Section: Discussionsupporting

confidence: 87%

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

Lenfant

Pizzato

Liang

et al. 2003

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

The non-classical major histocompatibility complex class I molecule HLA-G is expressed mainly by extravillous trophoblasts at the materno-foetal interface. HLA-G has been found to bind endogenously processed nonameric peptides but its function as a restriction element for a cytotoxic T cell response to viruses with tropism for trophoblastic cells has never been demonstrated. In this study, candidate viral peptides derived from human cytomegalovirus (HCMV) pp65 (UL83), which stabilized the HLA-G molecule on HLA-G-transfected T2 cells, were identified. The specific antipp65 cytotoxic T lymphocyte (CTL) response restricted by HLA-G in triple transgenic mice (HLA-G, human b2m, human CD8a) was then investigated by injection of dendritic cells loaded with synthetic pp65-derived peptides or by infection with canarypox virus expressing pp65. Results showed that CTLs from HLA-G mice have the capacity to kill target cells either infected with recombinant vaccinia viruses expressing pp65 or loaded with specific pp65-derived peptides using HLA-G as an antigen-presenting molecule. It was also demonstrated that these HLA-G-restricted pp65-specific T cells are able to kill the human astrocytoma cell line U373, which was transfected with HLA-G and infected with HCMV. Moreover, using HLA-G tetramers refolded with a synthetic pp65-derived peptide, peptide-specific CD8 + cells restricted by HLA-G have been detected in vivo. These findings provide the first evidence that HLA-G can select anti-HCMV-restricted CTLs in vivo, although the potency of this cytolytic response is limited (20-25 %). The weak HLA-Grestricted anti-HCMV response is probably due to HLA-G-mediated inhibitory signals on the development of an antiviral CTL response. INTRODUCTIONDuring pregnancy, the placenta is the first barrier that protects the foetus from pathogens. It is of relevance, therefore, that trophoblast cells in placental tissues lack major histocompatibility (MHC) class I expression. These highly polymorphic MHC molecules, HLA-A and HLA-B, play a central role in the detection and elimination of infected cells by CD8 + T cells and natural killer (NK) cells. However, despite the general lack of classical MHC molecules, extravillous trophoblasts, a subpopulation of trophoblasts that is in direct contact with maternal cells, express low levels of HLA-C and at a higher extent, the non-classical HLA-Ib molecules HLA-G and HLA-E (Kovats et al., 1990;Le Bouteiller et al., 1999;King et al., 2000), which are accompanied by abundant expression of transporter-associated proteins (TAP) (Clover et al., 1995). The non-classical HLA-Ib molecule HLA-E binds preferentially to leader peptides of many MHC class I molecules (Braud et al., 1998;Lee et al., 1998) and these complexes function as ligands for CD94/NKG2 receptors on NK cells . HLA-G molecules have a peptide-binding groove that is homologous to those of classical MHC class I molecules. In addition, HLA-G was shown to present nonameric peptides derived from a variety of intracellular proteins (Diehl et al., 199...

show abstract

Section: Discussionsupporting

confidence: 87%

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

Lenfant

Pizzato

Liang

et al. 2003

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Under immunosuppressive treatment, Qa-2 might protect the transplants from rejection by inhibiting the function of cells involved in graft rejection, thereby prolonging allograft survival. Some studies have reported that HLA-G inhibits the cytotoxic activity of CD8 + T cells and NK cells (29), the proliferation of CD4 + T cells (30), the cell-cycle progression of alloreactive T cells (31) and the maturation of antigen-presenting cells (32). Some investigators found that HLA-G efficiently induced immunosuppressive T cells (33).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of HNF-1α Mutations Associated with Familial Young-Onset Diabetes on Target Gene Regulation

Galán

García-Herrero

Azriel

et al. 2010

Mol Med

View full text Add to dashboard Cite

“…For instance, HLA-G1 protects targets from both NK cell-and CTLmediated lysis, and only few HLA-G1-positive cells are required to exert significant inhibitory effect [15,18]. Furthermore, HLA-G has been shown to impair the maturation of dendritic cells, resulting in prolonged allogeneic skin graft survival [19]. HLA-G leader peptide stabilizes the cell-surface expression of another non-classical HLA class I inhibitory molecule, HLA-E [20].…”

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

View full text Add to dashboard Cite

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.

show abstract

HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune inhibitory receptor

Cited by 128 publications

References 32 publications

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

Differential Effects of HNF-1α Mutations Associated with Familial Young-Onset Diabetes on Target Gene Regulation

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

Contact Info

Product

Resources

About

HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune inhibitory receptor

Cited by 128 publications

References 32 publications

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

Differential Effects of HNF-1α Mutations Associated with Familial Young-Onset Diabetes on Target Gene Regulation

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

Contact Info

Product

Resources

About

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