Peripheral regulatory CD8+CD28-KLRG1+ T cells as markers of disease and treatment response in rheumatoid arthritis.

CD3+CD8+CD28- cells are increased in the periphery and tissues of rheumatoid arthritis (RA) patients. The aim of this study was to characterise CD3+CD8+CD28- cells for the presence of cell surface receptors that regulate immune activation and function and to track their presence in a disease model of RA. Cell surface receptors expressed by CD3+CD8+CD28- cells were then related to serological and clinical disease parameters to establish whether these cells are prognostic of a clinical response to conventional DMARDs. Method. Using healthy donor peripheral blood mononuclear (PBMC) cell surface expression of >50 candidate markers were tested using flow cytometry and compared against CD28 expression. The prevalence of cells expressing the most suitable candidate was investigated in the collagen induced arthritis (CIA) and the antigen-induced arthritis (AIA) models. Fifty RA patients were recruited from University Hospital of Wales (UHW) rheumatology outpatient clinic. Clinical and serological markers of inflammation were noted, and PBMC were analysed using flow cytometry +/- in vitro stimulation. Results. CD3+CD8+CD28- T cells express CD244, CD57, CX3CR1 and KLRG1. The strongest inverse correlate of CD28 expression was KLRG1. CD3+CD8+CD28-KLRG1+ cells were elevated in experimental models of RA. Notably, Il-10-deficiency was linked with exacerbated arthritis and an increase in the number of CD3+CD8+CD28-KLRG1+ cells, suggesting a regulatory role for Il-10 in their development or survival. In RA patients, CD3+CD8+CD28-KLRG1+ cells correlate with ACPA, RF and ESR, and produce more IL-10 than controls. Finally, these cells are higher in early arthritis patients that do not respond to treatment with synthetic DMARDs at six months. Conclusion. KLRG1 is a marker for regulatory CD3+CD8+CD28- cells. The presence of CD3+CD8+CD28-KLRG1+ cells increases with certain measures of disease, and is indicative of poor treatment response to DMARDs in early arthritis.

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Polymyositis, Topological Proteomics Technology and Paradigm for Cell Invasion Dynamics

Journal of Theoretical Medicine ◽

10.1080/10273660290015224 ◽

2002 ◽

Vol 4 (1) ◽

pp. 75-84 ◽

Cited By ~ 8

Author(s):

Walter Schubert

Keyword(s):

T Cells ◽

T Cell ◽

Cell Surface ◽

Cell Invasion ◽

Large Scale ◽

Expression Patterns ◽

Inflammatory Myopathy ◽

Protein Profiling ◽

Cell Surface Receptors ◽

Surface Receptors

Polymyositis is an inflammatory myopathy characterized by muscle invasion of T-cells penetrating the basal lamina and displacing the plasma membrane of normal muscle fibers. This investigation presents a technology for the direct mapping of protein networks involved in T-cell invasionin situ. Simultaneous localization of 17 adhesive cell surface receptors reveals 18 different combinatorial expression patterns (CEP), which are unique for the T-cell invasion process in muscle tissue. Each invasion step can be assigned to specific CEP on the surface of individual T-cells. This indicates, that the T-cell invasion is enciphered combinatorially in the T-cells' adhesive cell surface proteome fraction. Given 217possible combinations, the T-cell appears to have at its disposal a highly non-random restricted repertoire to specify migratory pathways at the cell surface. These higher-level order functions in the cellular proteome cannot be detected by large-scale protein profiling techniques from tissue homogenates. High-throughput whole cell mapping machines working on structurally intact tissues, as shown here, will allow to measure how cells of different origin (immune cells, tumor cells) combine cell surface receptors to encipher specificity and selectivity for interactions.

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Green- and red-fluorescent nanospheres for the detection of cell surface receptors by flow cytometry

Journal of Immunological Methods ◽

10.1016/s0022-1759(98)00121-5 ◽

1998 ◽

Vol 219 (1-2) ◽

pp. 57-68 ◽

Cited By ~ 27

Author(s):

Mahesh K. Bhalgat ◽

Rosaria P. Haugland ◽

Jeffrey S. Pollack ◽

Sharon Swan ◽

Richard P. Haugland

Keyword(s):

Flow Cytometry ◽

Cell Surface ◽

Cell Surface Receptors ◽

Surface Receptors

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A statistical theory for flow cytometry profiles in terms of the binding of ligands to cell surface receptors and changes in gene expression

Journal of Mathematical Biology ◽

10.1007/bf00160497 ◽

1996 ◽

Vol 34 (3) ◽

pp. 271-296

Author(s):

W. G. Bardsley ◽

E. K. Kyprianou

Keyword(s):

Gene Expression ◽

Flow Cytometry ◽

Statistical Theory ◽

Cell Surface ◽

Cell Surface Receptors ◽

Surface Receptors

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Tyrosine phosphorylation of CD6 by stimulation of CD3: augmentation by the CD4 and CD2 coreceptors.

Journal of Experimental Medicine ◽

10.1084/jem.177.1.219 ◽

1993 ◽

Vol 177 (1) ◽

pp. 219-223 ◽

Cited By ~ 39

Author(s):

S Wee ◽

G L Schieven ◽

J M Kirihara ◽

T T Tsu ◽

J A Ledbetter ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Surface ◽

T Cell Activation ◽

Intracellular Signaling ◽

Cell Activation ◽

Cell Receptor ◽

Surface Proteins ◽

Cell Surface Receptors ◽

Surface Receptors

When T cells are activated via the T cell receptor (TCR) complex a number of cellular substrates, including some cell surface proteins, become phosphorylated on tyrosine (Tyr) residues. Phosphorylation of cytoplasmic Tyr renders these cell surface receptors competent to interact with proteins that link cell surface receptors to protein in the intracellular signaling pathways. Here we show that Tyr residues in the cytoplasmic domain of CD6 become phosphorylated upon T cell activation via the TCR complex. Tyr phosphorylation was observed when the T cells were activated by crosslinking CD3 or by cocrosslinking CD3 with CD2 or CD4, but not when the cells were stimulated by crosslinking CD2, CD4, or CD28 alone. Unlike other Tyr kinase substrates, such as the phospholipase C gamma 1-associated pp35/36 protein, whose level of Tyr phosphorylation is highest when T cells are activated by cocrosslinking CD3 with CD2, the levels of CD6 Tyr phosphorylation are highest when T cells were activated by cocrosslinking CD3 with CD4.

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Diversity of receptor expression in central and peripheral mouse neurons estimated from single cell RNA sequencing

10.1101/2021.01.22.427766 ◽

2021 ◽

Author(s):

Andi Wangzhou ◽

Candler Paige ◽

Pradipta R. Ray ◽

Gregory Dussor ◽

Theodore J. Price

Keyword(s):

T Cells ◽

Cell Surface ◽

Single Cell ◽

Rna Sequencing ◽

Sympathetic Neurons ◽

Receptor Expression ◽

Cell Surface Receptors ◽

Surface Receptors ◽

Single Cell Rna Sequencing ◽

Cns Neurons

AbstractBecause somatosensory PNS neurons, in particular nociceptors, are specially tuned to be able to detect a wide variety of both exogenous and endogenous signals, it is widely assumed that these neurons express a greater variety of receptor genes. Because cells detect such signals via cell surface receptors, we sought to formally test the hypothesis that PNS neurons might express a broader array of cell surface receptors than CNS neurons using existing single cell RNA sequencing resources from mouse. We focused our analysis on ion channels, G-protein coupled receptors (GPCRS), receptor tyrosine kinase and cytokine family receptors. In partial support of our hypothesis, we found that mouse PNS somatosensory, sympathetic and enteric neurons and CNS neurons have similar receptor expression diversity in families of receptors examined, with the exception of GPCRs and cytokine receptors which showed greater diversity in the PNS. Surprisingly, these differences were mostly driven by enteric and sympathetic neurons, not by somatosensory neurons or nociceptors. Secondary analysis revealed many receptors that are very specifically expressed in subsets of PNS neurons, including some that are unique among neurons for nociceptors. Finally, we sought to examine specific ligand-receptor interactions between T cells and PNS and CNS neurons. Again, we noted that most interactions between these cells are shared by CNS and PNS neurons despite the fact that T cells only enter the CNS under rare circumstances. Our findings demonstrate that both PNS and CNS neurons express an astonishing array of cell surface receptors and suggest that most neurons are tuned to receive signals from other cells types, in particular immune cells.

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