Fully competent dendritic cells as inducers of T cell anergy in autoimmunity

Quaratino, Sonia; Duddy, L. P.; Londei, Marco

doi:10.1073/pnas.190204697

Cited by 42 publications

(31 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Different regulatory T cells have been reported and they are known to differentiate upon the encounter with immature DC (53,55). However, fully competent DC were also found to be inducers of T cell anergy when presenting a self-epitope with altered peptide ligand features (56). Whether IL-10 produced in BM-transplanted mice infused with Candidapulsed DC may serve to support the growth of regulatory T cells preventing donor Th1 alloreactivity remains a working hypothesis, although it may help to explain the long-term, disease-free survival of the mice.…”

Section: Figurementioning

confidence: 99%

Dendritic Cells Pulsed with Fungal RNA Induce Protective Immunity toCandida albicansin Hematopoietic Transplantation

Bacci

Montagnoli

Perruccio

et al. 2002

The Journal of Immunology

120

View full text Add to dashboard Cite

Immature myeloid dendritic cells (DC) phagocytose yeasts and hyphae of the fungus Candida albicans and induce different Th cell responses to the fungus. Ingestion of yeasts activates DC for production of IL-12 and Th1 priming, while ingestion of hyphae induces IL-4 production and Th2 priming. In vivo, generation of antifungal protective immunity is induced upon injection of DC ex vivo pulsed with Candida yeasts but not hyphae. In the present study we sought to determine the functional activity of DC transfected with yeast or hyphal RNA. It was found that DC, from either spleens or bone marrow, transfected with yeast, but not hyphal, RNA 1) express fungal mannoproteins on their surface; 2) undergo functional maturation, as revealed by the up-regulated expression of MHC class II Ags and costimulatory molecules; 3) produce IL-12 but no IL-4; 4) are capable of inducing Th1-dependent antifungal resistance when delivered s.c. in vivo in nontransplanted mice; and 5) provide protection against the fungus in allogeneic bone marrow-transplanted mice, by accelerating the functional recovery of Candida-specific IFN-γ-producing CD4+ donor lymphocytes. These results indicate the efficacy of DC pulsed with Candida yeasts or yeast RNA as fungal vaccines and point to the potential use of RNA-transfected DC as anti-infective vaccines in conditions that negate the use of attenuated microorganisms or in the case of poor availability of protective Ags.

show abstract

Section: Figurementioning

confidence: 99%

Dendritic Cells Pulsed with Fungal RNA Induce Protective Immunity toCandida albicansin Hematopoietic Transplantation

Bacci

Montagnoli

Perruccio

et al. 2002

The Journal of Immunology

120

View full text Add to dashboard Cite

show abstract

“…Later it has became evident that dendritic cells (DCs) can also act as a very potent APC [3,4]. They express large amounts of surface class II HLA antigens [5] particularly HLA-DR and lack macrophage differentiation antigens like CD14 or CD68 [6,7]. The importance of co-stimulatory signals has been highlighted by several studies [8].…”

Section: Introductionmentioning

confidence: 99%

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Bălănescu

Radu

Nat

et al. 2002

J Cellular Molecular Medi

View full text Add to dashboard Cite

Dendritic cells (DCs) in the rheumatoid arthritis (RA) joint mediate the immunopathological process and act as a potent antigen presenting cell. We compared the expression of co‐stimulatory and adhesion molecules on DCs in RA patients versus controls with traumatic joint lesions and evalulated the correlation between the immunophenotypical presentation of DCs and the clinical status of the disease. Samples of peripheral venous blood, synovial fluid (SF) and synovial tissue (ST) were obtained from 10 patients with RA at the time of hip or knee replacement and from 9 control patients with knee arthroscopy for traumatic lesions. Clinical status was appreciated using the DAS28 score. Blood, SF and dissociated ST cell populations were separated by centrifugation and analyzed by flow cytometry. Cells phenotypes were identified using three‐color flow cytometry analysis for the following receptors HLA‐DR, CD80, CD83, CD86, CD11c, CD18, CD54, CD58, CD3, CD4, CD8, CD19, CD20, CD14, CD16, CD56. HLA‐DR molecules, co‐stimulatory receptors CD80, CD86, CD83 and adhesion molecules CD18, CD11c, CD54, CD58, were analyzed by two‐color immunofluorescence microscopy on ST serial sections. In patients with active RA (DAS28>5.1) we found a highly differentiated subpopulation of DCs in the ST and SF that expressed an activated phenotype (HLA‐DR, CD86+, CD80+, CD83+, CD11c+, CD54+, CD58+). No differences were found between circulating DCs from RA patients and control patients. Our data suggest an interrelationship between clinical outcome and the immunophenotypical presentation of DCs. Clinical active RA (DAS28>5.1) is associated with high incidence of activated DCs population in the ST and SF as demonstrated by expression of adhesion and co‐stimulatory molecules.

show abstract

“…This TPO epitope is presented in vivo only upon endogenous processing in thyroid epithelial cells and in vitro in TPOtransduced cells such as EBV-transformed B cells (21). We have demonstrated that T cell clone 37 is not stimulated by fully competent DCs pulsed with TPO, but, on the contrary, it is anergized by a tolerogenic epitope presented by DCs (24).…”

Section: The Human Autoantibodies Do Not Allow the Presentation Of A mentioning

confidence: 86%

“…These T cell clones were also instrumental in defining and characterizing a human cryptic epitope of TPO (21) involved in the development of autoimmunity (22). This cryptic epitope was presented when TPO was expressed as a surface molecule (21), as normally occurs in vivo on thyroid epithelial cells (23), but not when DC or other professional APC were loaded with exogenous TPO (21,24).…”

Section: And B Cells Can Communicate By Exchanging Information Via Thmentioning

confidence: 99%

See 1 more Smart Citation

Human Autoantibodies Modulate the T Cell Epitope Repertoire but Fail to Unmask a Pathogenic Cryptic Epitope

Quaratino

Ruf

Osman

et al. 2005

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Abs can tune the responses of Ag-specific T cells by influencing the nature of the epitope repertoire displayed by APCs. We explored the interaction between human self-reactive T cells and human monoclonal autoantibodies from combinatorial Ig-gene libraries derived from autoimmune thyroiditis patients and specific for the main autoantigen thyroid peroxidase (TPO). All human mAbs extensively influenced the T cell epitope repertoire recognized by different TPO-specific T cell clones. The action of the human mAbs was complex, because sometimes the same Ab suppressed or enhanced the epitopes recognized by the 10 different TPO-specific T cell clones. The human mAbs could modulate the epitope repertoire when TPO was added exogenously and when expressed constitutively on the surface of APCs. However, they could not unmask an immunodominant cryptic TPO epitope. In this study, we show that human autoantibodies influence the activity of self-reactive T cells and prove their relevance in concealing or exposing epitopes recognized by self-reactive T cells. However, our results further stress the biological significance of the immunodominant cryptic epitope we have defined and its potential importance in the evolution of autoimmunity.

show abstract

Fully competent dendritic cells as inducers of T cell anergy in autoimmunity

Cited by 42 publications

References 40 publications

Dendritic Cells Pulsed with Fungal RNA Induce Protective Immunity toCandida albicansin Hematopoietic Transplantation

Dendritic Cells Pulsed with Fungal RNA Induce Protective Immunity toCandida albicansin Hematopoietic Transplantation

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Human Autoantibodies Modulate the T Cell Epitope Repertoire but Fail to Unmask a Pathogenic Cryptic Epitope

Contact Info

Product

Resources

About