Coinhibitory Molecules in Autoimmune Diseases

Watanabe, Norihiko; Nakajima, Hiroshi

doi:10.1155/2012/269756

Cited by 40 publications

(34 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abatacept, a fusion protein composed of the Fc fragment of human IgG1 linked to the extracellular domain of CTLA-4, has shown efficacy in a broad spectrum of RA patients from early stage to refractory diseases that are resistant to TNF blockers (81–84). …”

Section: Cd8+ Ts Cells In Autoimmune Diseasesmentioning

confidence: 99%

Molecular and Cellular Characterization of Human CD8 T Suppressor Cells

Chang

et al. 2016

Front. Immunol.

View full text Add to dashboard Cite

Bidirectional interactions between dendritic cells and Ag-experienced T cells initiate either a tolerogenic or immunogenic pathway. The outcome of these interactions is of crucial importance in malignancy, transplantation, and autoimmune diseases. Blockade of costimulation results in the induction of T helper cell anergy and subsequent differentiation of antigen-specific CD8+ T suppressor/regulatory cells (Ts). Ts, primed in the presence of inhibitory signals, exert their inhibitory function in an antigen-specific manner, a feature with tremendous clinical potential. In transplantation or autoimmunity, antigen-specific Ts can enforce tolerance to auto- or allo-antigens, while otherwise leaving the immune response to pathogens uninhibited. Alternatively, blockade of inhibitory receptors results in the generation of cytolytic CD8+ T cells, which is vital toward defense against tumors and viral diseases. Because CD8+ T cells are MHC Class I restricted, they are able to recognize HLA-bound antigenic peptides presented not only by APC but also on parenchymal cells, thus eliciting or suppressing auto- or allo-immune reactions.

show abstract

Section: Cd8+ Ts Cells In Autoimmune Diseasesmentioning

confidence: 99%

Molecular and Cellular Characterization of Human CD8 T Suppressor Cells

Chang

et al. 2016

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…As with CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and BTLA (B-and T-lymphocyte attenuator), a major function of PD-1 is to prevent the activated T cells from becoming overzealous, leading to adverse inflammatory responses and organ damage (22)(23)(24). PD-1 is a membrane protein of the CD28 family.…”

mentioning

confidence: 99%

“…PD-1 is a membrane protein of the CD28 family. It is expressed on the surfaces of many immune cells, including CD4 ϩ T cells, CD8 ϩ T cells, NK T cells, B cells, and monocytes (22,24,25). Its ligand PD-L1 (CD274), also called B7 homolog 1 (B7-H1), is a type I transmembrane protein and is constitutively expressed on T cells, B cells, macrophages, and dendritic cells (22,24,25).…”

mentioning

confidence: 99%

“…It is expressed on the surfaces of many immune cells, including CD4 ϩ T cells, CD8 ϩ T cells, NK T cells, B cells, and monocytes (22,24,25). Its ligand PD-L1 (CD274), also called B7 homolog 1 (B7-H1), is a type I transmembrane protein and is constitutively expressed on T cells, B cells, macrophages, and dendritic cells (22,24,25). During persistent antigen exposure, antigen-specific CD8 ϩ T cells may lose their effector functions, such as proliferation and cytokine production; this phenomenon is referred to as CD8 ϩ T-cell exhaustion (26).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Myeloid-Derived Suppressor Cells Impair Alveolar Macrophages through PD-1 Receptor Ligation during Pneumocystis Pneumonia

2015

View full text Add to dashboard Cite

Myeloid-derived suppressor cells (MDSCs) were recently found to accumulate in the lungs during Pneumocystis pneumonia (PcP). Adoptive transfer of these cells caused lung damage in recipient mice, suggesting that MDSC accumulation is a mechanism of pathogenesis in PcP. In this study, the phagocytic activity of alveolar macrophages (AMs) was found to decrease by 40% when they were incubated with MDSCs from Pneumocystis-infected mice compared to those incubated with Gr-1 ؉ cells from the bone marrow of uninfected mice. The expression of the PU.1 gene in AMs incubated with MDSCs also was decreased. This PU.1 downregulation was due mainly to decreased histone 3 acetylation and increased DNA methylation caused by MDSCs. MDSCs were found to express high levels of PD-L1, and alveolar macrophages (AMs) were found to express high levels of PD-1 during PcP. Furthermore, PD-1 expression in AMs from uninfected mice was increased by 18-fold when they were incubated with MDSCs compared to those incubated with Gr-1 ؉ cells from the bone marrow of uninfected mice. The adverse effects of MDSCs on AMs were diminished when the MDSCs were pretreated with anti-PD-L1 antibody, suggesting that MDSCs disable AMs through PD-1/PD-L1 ligation during PcP.

show abstract

“…Polymorphisms in CTLA-4 have been linked to diabetes mellitus, Hashimoto's thyroiditis, celiac disease, and primary biliary cirrhosis (13). It has been suggested that in the presence of these polymorphisms the inhibitory effect of CTLA-4 is impaired (12).…”

mentioning

confidence: 99%

Cytotoxic-T-Lymphocyte Antigen 4 Receptor Signaling for Lymphocyte Adhesion Is Mediated by C3G and Rap1

Kloog

Mor

2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

bT-lymphocyte adhesion plays a critical role in both inflammatory and autoimmune responses. The small GTPase Rap1 is the key coordinator mediating T-cell adhesion to endothelial cells, antigen-presenting cells, and virus-infected cells. We describe a signaling pathway, downstream of the cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor, leading to Rap1-mediated adhesion. We identified a role for the Rap1 guanine nucleotide exchange factor C3G in the regulation of T-cell adhesion and showed that this factor is required for both T-cell receptor (TCR)-mediated and CTLA-4-mediated T-cell adhesion. Our data indicated that C3G translocates to the plasma membrane downstream of TCR signaling, where it regulates activation of Rap1. We also showed that CTLA-4 receptor signaling mediates tyrosine phosphorylation in the C3G protein, and that this is required for augmented activation of Rap1 and increased adhesion mediated by leukocyte function-associated antigen type 1 (LFA-1). Zap70 is required for C3G translocation to the plasma membrane, whereas the Src family member Hck facilitates C3G phosphorylation. These findings point to C3G and Hck as promising potential therapeutic targets for the treatment of T-cell-dependent autoimmune disorders.

show abstract

Coinhibitory Molecules in Autoimmune Diseases

Cited by 40 publications

References 81 publications

Molecular and Cellular Characterization of Human CD8 T Suppressor Cells

Molecular and Cellular Characterization of Human CD8 T Suppressor Cells

Myeloid-Derived Suppressor Cells Impair Alveolar Macrophages through PD-1 Receptor Ligation during Pneumocystis Pneumonia

Cytotoxic-T-Lymphocyte Antigen 4 Receptor Signaling for Lymphocyte Adhesion Is Mediated by C3G and Rap1

Contact Info

Product

Resources

About