scholarly journals Expression of inhibitory receptors on CD4+ and CD8+ T cells from healthy Colombian donors

2012 ◽  
Vol 17 (1) ◽  
pp. 35
Author(s):  
Alejandra Rico- Lombana Rico- Lombana ◽  
Jose Mateus ◽  
Paola Lasso ◽  
John Mario González ◽  
Concepción Judith Puerta ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Inhibitory Receptors ◽  
Peripheral Blood Mononuclear ◽  
Programmed Death ◽  
Significant Difference ◽  
Programmed Death 1

<p>T cell activation involves positive cellular signals that promote effector functions and negative signals that contribute to the regulation of these responses. These regulatory signals are generated upon activation of receptors on T cells that include CD160, 2B4, Programmed Death-1 and CTLA-4. <strong>Objective</strong>. To evaluate the expression of inhibitory receptors like CD160, 2B4, Programmed Death-1 and CTLA-4 on CD4+ and CD8+ T cells from healthy Colombian donors. <strong>Materials and methods</strong>. Peripheral blood mononuclear cells from 30 healthy donors from Bogotá (Colombia) were obtained via Ficoll-Hypaque density gradient and cells were stained with specific conjugated antibodies previously titrated. <strong>Results</strong>. The CD160, 2B4, and Programmed Death-1 inhibitory markers were detected on CD4+ T cells<br />with expression levels of 0.35%, 1.04%, and 1.35%, respectively. On CD8+ T cells, these markers were expressed at higher levels: 16%, 8.97%, and 4.3%, respectively. In contrast to the other receptors, CTLA-4 frequency of expression showed no significant difference between CD4+ (1.56%) and CD8+ (1.53%) T cells. Frequency of CD160/2B4 and CTLA-4/ Programmed Death-1 coexpression was 0.18% and 0.09% on CD4+ cells, and 4.02% and 0.2% on CD8+ T cells. <strong>Conclusions</strong>. This is the first report showing the frequency of inhibitory receptors such as CD160, 2B4, Programmed Death-1, and CTLA-4 on CD4+ and CD8+ T cells from healthy Colombian donors. Our findings serve as a baseline for the analysis and comparison of these receptors in Colombian populations with different disease conditions.</p><p><br /><strong>Key words</strong>: inhibitory receptors, T cells</p>

scholarly journals Differential effects of IL-21 and IL-15 on perforin expression, lysosomal degranulation, and proliferation in CD8 T cells of patients with human immunodeficiency virus-1 (HIV)

Blood ◽  
2006 ◽  
Vol 109 (9) ◽  
pp. 3873-3880 ◽  
Author(s):  
Lesley White ◽  
Subramaniam Krishnan ◽  
Natasa Strbo ◽  
Huanliang Liu ◽  
Michael A. Kolber ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Highly Active Antiretroviral Therapy ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Peripheral Blood Mononuclear ◽  
Perforin Expression

Abstract An urgent need exists to devise strategies to augment antiviral immune responses in patients with HIV who are virologically well controlled and immunologically stable on highly active antiretroviral therapy (HAART). The objective of this study was to compare the immunomodulatory effects of the cytokines interleukin (IL)–21 with IL-15 on CD8 T cells in patients with HIV RNA of less than 50 copies/mL and CD4 counts greater than 200 cells/mm.3 Patient CD8 T cells displayed skewed maturation and decreased perforin expression compared with healthy controls. Culture of freshly isolated patient peripheral-blood mononuclear cells (PBMCs) for 5 hours to 5 days with IL-21 resulted in up-regulation of perforin in CD8 T cells, including memory and effector subsets and virus-specific T cells. IL-21 did not induce T-cell activation or proliferation, nor did it augment T-cell receptor (TCR)–induced degranulation. Treatment of patient PBMCs with IL-15 resulted in induction of perforin in association with lymphocyte proliferation and augmentation of TCR-induced degranulation. Patient CD8 T cells were more responsive to cytokine effects than the cells of healthy volunteers. We conclude that CD8 T cells of patients with HIV can be modulated by IL-21 to increase perforin expression without undergoing overt cellular activation. IL-21 could potentially be useful for its perforin-enhancing properties in anti-HIV immunotherapy.

Reproducibility and Robustness of the Xcellerate III Process for the GMP Manufacture of Xcellerated T Cells™ for Infusion into CLL Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4995-4995
Author(s):  
Lisa Hami ◽  
Cherie Green ◽  
Katharine Miller ◽  
Stewart Craig
Keyword(s):  
T Cells ◽  
Cell Viability ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Total Cell ◽  
Cell Yield ◽  
P Value ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference

Abstract Autologous peripheral blood mononuclear cells (PBMC) cryopreserved from a leukapheresis collection comprise the starting cellular source for the Wave® Bioreactor-based Xcellerate III Process [Hami et al, Bioprocessing Journal2003: 2; 23–32] used for the GMP manufacture of Xcellerated T Cells. For an ongoing clinical trial, n=13 patients have been infused with products manufactured from PBMC cryopreserved and stored in the vapor phase of liquid nitrogen (LN2) for 2–9 days before use in the Xcellerate III Process. This clinical protocol was recently amended to allow patients to receive a 2nd infusion of Xcellerated T Cells. To date, 2nd products have been manufactured for 11 of the CLL patients using the original PBMC that had been stored cryopreserved for up to 7 months from collection. Comparison of the processes for the manufacture of 1st (n=13) and 2nd (n=11) infusion products shows: • No significant difference in the in-process T cell activation as determined by increase in cell size, up-regulation of CD25 & up-regulation of CD154 expression (refer to Figure 1). Figure Figure • The total cell yield for 2nd infusion products is within one (1) standard deviation of the average for the manufacture of the 1st infusion product (refer to Table 1). • No significant difference in cell viability, CD3+ purity, or CD4:CD8 ratio for the final Xcellerated T Cells product (refer to Table 1). Table 1. Final Product Characteristics Final Product (Day 13) Average±S.D. p value 1st Infusion (n=13) 2nd Infusion (n=11) Total Cell Yield (x109) 0.01 137 ± 35 104 ± 17 Cell Viability (%) 0.15 93.5 ± 3.4 91.6 ± 2.4 CD3+ Purity (%) <0.001 98.4 ± 1.1 99.0 ± 0 CD4:CD8 Ratio 0.32 8.5 ± 7.7 5.7 ± 4.5 These data demonstrate high reproducibility and robustness of the Xcellerate III Process when using PBMC from the same leukapheresis collection in sequential processing runs. In addition, these data demonstrate that cryopreserved PBMC can be stored for many months prior to their use as the starting material in the Xcellerate III Process. Xcyte™, Xcyte Therapies™, Xcellerate™, Xcellerated T Cells™ and the circle logo are trademarks of Xcyte Therapies, Inc.

scholarly journals Deoxynivalenol Affects Proliferation and Expression of Activation-Related Molecules in Major Porcine T-Cell Subsets

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 644 ◽  
Author(s):  
Vatzia ◽  
Pierron ◽  
Saalmüller ◽  
Mayer ◽  
Gerner
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Animal Feed ◽  
Γδ T Cells ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear

The Fusarium mycotoxin deoxynivalenol (DON) contaminates animal feed worldwide. In vivo, DON modifies the cellular protein synthesis, thereby also affecting the immune system. However, the functional consequences of this are still ill-defined. In this study, peripheral blood mononuclear cells from healthy pigs were incubated with different DON concentrations in the presence of Concanavalin A (ConA), a plant-derived polyclonal T-cell stimulant. T-cell subsets were investigated for proliferation and expression of CD8α, CD27, and CD28, which are involved in activation and costimulation of porcine T cells. A clear decrease in proliferation of all ConA-stimulated major T-cell subsets (CD4+, CD8+, and γδ T cells) was observed in DON concentrations higher than 0.4 µM. This applied in particular to naïve CD4+ and CD8+ T cells. From 0.8 μM onwards, DON induced a reduction of CD8α (CD4+) and CD27 expression (CD4+ and CD8+ T cells). CD28 expression was diminished in CD4+ and CD8+ T cells at a concentration of 1.6 µM DON. None of these effects were observed with the DON-derivative deepoxy-deoxynivalenol (DOM-1) at 16 µM. These results indicate that DON reduces T-cell proliferation and the expression of molecules involved in T-cell activation, providing a molecular basis for some of the described immunosuppressive effects of DON.

scholarly journals Endogenous retrovirus-encoded Syncytin-2 contributes to exosome-mediated immunosuppression of T cells†

2019 ◽  
Author(s):  
Adjimon G Lokossou ◽  
Caroline Toudic ◽  
Phuong Trang Nguyen ◽  
Xavier Elisseeff ◽  
Amandine Vargas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Map Kinases ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Endogenous Retrovirus ◽  
Jurkat Cells ◽  
Peripheral Blood Mononuclear ◽  
Interfering Rna

Abstract Modulation of the activation status of immune cell populations during pregnancy depends on placental villous cytotrophoblast (VCT) cells and the syncytiotrophoblast (STB). Failure in the establishment of this immunoregulatory function leads to pregnancy complications. Our laboratory has been studying Syncytin-2 (Syn-2), an endogenous retroviral protein expressed in placenta and on the surface of placental exosomes. This protein plays an important role not only in STB formation through its fusogenic properties, but also through its immunosuppressive domain (ISD). Considering that Syn-2 expression is importantly reduced in preeclamptic placentas, we were interested in addressing its possible immunoregulatory effects on T cells. Activated Jurkat T cells and peripheral blood mononuclear cells (PBMCs) were treated with monomeric or dimerized version of a control or a Syn-2 ISD peptide. Change in phosphorylation levels of ERK1/2 MAP kinases was selectively noted in Jurkat cells treated with the dimerized ISD peptide. Upon incubation with the dimerized Syn-2 ISD peptide, significant reduction in Th1 cytokine production was further demonstrated by ELISA and Human Th1/Th2 Panel Multi-Analyte Flow Assay. To determine if exosome-associated Syn-2 could also be immunosuppressive placental exosomes were incubated with activated Jurkat and PBMCs. Quantification of Th1 cytokines in the supernatants revealed severe reduction in T cell activation. Interestingly, exosomes from Syn-2-silenced VCT incubated with PBMCs were less suppressive when compared with exosome derived from VCT transfected with control small interfering RNA (siRNA). Our results suggest that Syn-2 is an important immune regulator both locally and systemically, via its association with placental exosomes.

scholarly journals DNAM1 and TIGIT balance the T cell response, with low T cell TIGIT expression corresponding to inflammation in psoriatic disease

2020 ◽  
Author(s):  
M E Jacobs ◽  
J N Pouw ◽  
M A Olde Nordkamp ◽  
T R D J Radstake ◽  
E F A Leijten ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Inverse Correlation ◽  
T Cell Response ◽  
Peripheral Blood Mononuclear ◽  
Psoriatic Disease

Abstract Background Signals at the contact site of antigen-presenting cells (APCs) and T cells help orchestrate the adaptive immune response. CD155 on APCs can interact with the stimulatory receptor DNAM1 or inhibitory receptor TIGIT on T cells. The CD155/DNAM1/TIGIT axis is under extensive investigation as immunotherapy target in inflammatory diseases including cancer, chronic infection and autoimmune diseases. We investigated a possible role for CD155/DNAM1/TIGIT signaling in psoriatic disease. Methods By flow cytometry we analyzed peripheral blood mononuclear cells of patients with psoriasis (n=20) or psoriatic arthritis (n=21), and healthy individuals (n=7). We measured CD155, TIGIT and DNAM1 expression on leukocyte subsets and compared activation-induced cytokine production between CD155-positive and -negative APCs. We assessed the effects of TIGIT and DNAM1 blockade on T cell activation, and related the expression of CD155/DNAM1/TIGIT axis molecules to measures of disease activity. Results High CD155 expression associates with TNF production in myeloid and plasmacytoid dendritic cells (DC). In CD1c+ myeloid DC, activation-induced CD155 expression associates with increased HLA-DR expression. CD8 T cells - but not CD4 T cells - express high levels of TIGIT. DNAM1 blockade decreases T cell pro-inflammatory cytokine production, while TIGIT blockade increased T cell proliferation. Finally, T cell TIGIT expression shows an inverse correlation with inflammation biomarkers in psoriatic disease. Conclusion CD155 is increased on pro-inflammatory APCs, while the receptors DNAM1 and TIGIT expressed on T cells balance the inflammatory response by T cells. In psoriatic disease, low TIGIT expression on T cells is associated with systemic inflammation.

scholarly journals Decreased Expression of the CD3ζ Chain in T Cells Infiltrating the Synovial Membrane of Patients with Osteoarthritis

2004 ◽  
Vol 11 (1) ◽  
pp. 195-202 ◽  
Author(s):  
Lazaros I. Sakkas ◽  
George Koussidis ◽  
Efthimios Avgerinos ◽  
John Gaughan ◽  
Chris D. Platsoucas
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
T Cell Stimulation ◽  
Inflammatory Infiltrates

ABSTRACT Osteoarthritis (OA) is a heterogeneous disease which rheumatologists consider to be noninflammatory. However, recent studies suggest that, at least in certain patients, OA is an inflammatory disease and that patients often exhibit inflammatory infiltrates in the synovial membranes (SMs) of macrophages and activated T cells expressing proinflammatory cytokines. We report here that the expression of CD3ζ is significantly decreased in T cells infiltrating the SMs of patients with OA. The CD3ζ chain is involved in the T-cell signal transduction cascade, which is initiated by the engagement of the T-cell antigen receptor and which culminates in T-cell activation. Double immunofluorescence of single-cell suspensions derived from the SMs from nine patients with OA revealed significantly increased proportions of CD3ε-positive (CD3ε+) cells compared with the proportions of CD3ζ-positive (CD3ζ+) T cells (means ± standard errors of the means, 80.48% ± 3.92% and 69.02% ± 6.51%, respectively; P = 0.0096), whereas there were no differences in the proportions of these cells in peripheral blood mononuclear cells (PBMCs) from healthy donors (94.73% ± 1.39% and 93.79% ± 1.08%, respectively; not significant). The CD3ζ+ cell/CD3ε+ cell ratio was also significantly decreased for T cells from the SMs of patients with OA compared with that for T cells from the PBMCs of healthy donors (0.84 ± 0.17 and 0.99 ± 0.01, respectively; P = 0.0302). The proportions of CD3ε+ CD3ζ+ cells were lower in the SMs of patients with OA than in the PBMCs of healthy donors (65.04% ± 6.7% and 90.81% ± 1.99%, respectively; P = 0.0047). Substantial proportions (about 15%) of CD3ε+ CD3ζ-negative (CD3ζ−) and CD3ε-negative (CD3ε−) CD3ζ− cells were found in the SMs of patients with OA. Amplification of the CD3ζ and CD3δ transcripts from the SMs of patients with OA by reverse transcriptase PCR consistently exhibited stronger bands for CD3δ cDNA than for CD3ζ cDNA The CD3ζ/CD3δ transcript ratio in the SMs of patients with OA was significantly lower than that in PBMCs from healthy controls (P < 0.0001). These results were confirmed by competitive MIMIC PCR. Immunoreactivities for the CD3ζ protein were detected in the SMs of 10 of 19 patients with OA, and they were of various intensities, whereas SMs from all patients were CD3ε+ (P = 0.0023). The decreased expression of the CD3ζ transcript and protein in T cells from the SMs of patients with OA relative to that of the CD3ε transcript is suggestive of chronic T-cell stimulation and supports the concept of T-cell involvement in OA.

scholarly journals Selection and T-cell antigenicity of synthetic long peptides derived from SARS-CoV-2

2022 ◽  
Vol 103 (1) ◽  
Author(s):  
Katarzyna Piadel ◽  
Amin Haybatollahi ◽  
Angus George Dalgleish ◽  
Peter Lawrence Smith
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
T Cell Responses ◽  
Hla Class I ◽  
Peripheral Blood Mononuclear ◽  
Cell Responses

The pandemic caused by SARS-CoV-2 has led to the successful development of effective vaccines however the prospect of variants of SARS-CoV-2 and future coronavirus outbreaks necessitates the investigation of other vaccine strategies capable of broadening vaccine mediated T-cell responses and potentially providing cross-immunity. In this study the SARS-CoV-2 proteome was assessed for clusters of immunogenic epitopes restricted to diverse human leucocyte antigen. These regions were then assessed for their conservation amongst other coronaviruses representative of different alpha and beta coronavirus genera. Sixteen highly conserved peptides containing numerous HLA class I and II restricted epitopes were synthesized from these regions and assessed in vitro for their antigenicity against T-cells from individuals with previous SARS-CoV-2 infection. Monocyte derived dendritic cells were generated from these peripheral blood mononuclear cells (PBMC), loaded with SARS-CoV-2 peptides, and used to induce autologous CD4+ and CD8+ T cell activation. The SARS-CoV-2 peptides demonstrated antigenicity against the T-cells from individuals with previous SARS-CoV-2 infection indicating that this approach holds promise as a method to activate anti-SAR-CoV-2 T-cell responses from conserved regions of the virus which are not included in vaccines utilising the Spike protein.

scholarly journals Hybrid nanocarriers incorporating mechanistically distinct drugs for lymphatic CD4+ T cell activation and HIV-1 latency reversal

2019 ◽  
Vol 5 (3) ◽  
pp. eaav6322 ◽  
Author(s):  
Shijie Cao ◽  
Sarah D. Slack ◽  
Claire N. Levy ◽  
Sean M. Hughes ◽  
Yonghou Jiang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Cell Model ◽  
Sustained Drug Release ◽  
Peripheral Blood Mononuclear ◽  
Low Cytotoxicity ◽  
Multiple Drugs

A proposed strategy to cure HIV uses latency-reversing agents (LRAs) to reactivate latent proviruses for purging HIV reservoirs. A variety of LRAs have been identified, but none has yet proven effective in reducing the reservoir size in vivo. Nanocarriers could address some major challenges by improving drug solubility and safety, providing sustained drug release, and simultaneously delivering multiple drugs to target tissues and cells. Here, we formulated hybrid nanocarriers that incorporate physicochemically diverse LRAs and target lymphatic CD4+ T cells. We identified one LRA combination that displayed synergistic latency reversal and low cytotoxicity in a cell model of HIV and in CD4+ T cells from virologically suppressed patients. Furthermore, our targeted nanocarriers selectively activated CD4+ T cells in nonhuman primate peripheral blood mononuclear cells as well as in murine lymph nodes, and substantially reduced local toxicity. This nanocarrier platform may enable new solutions for delivering anti-HIV agents for an HIV cure.

scholarly journals Rosetting T cells in Hodgkin lymphoma are activated by immunological synapse components HLA class II and CD58

Blood ◽  
2020 ◽  
Vol 136 (21) ◽  
pp. 2437-2441 ◽  
Author(s):  
Johanna Veldman ◽  
Lydia Visser ◽  
Magdalena Huberts-Kregel ◽  
Natasja Muller ◽  
Bouke Hepkema ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hodgkin Lymphoma ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Immunological Synapse ◽  
Class Ii ◽  
Rosette Formation ◽  
Peripheral Blood Mononuclear

Abstract A unique feature of Hodgkin lymphoma (HL) is the presence of CD4+ T cells that surround, protect, and promote survival of tumor cells. The adhesion molecules involved in this so-called T-cell rosetting are important components of the immunological synapse (IS). However, it is unknown whether this synapse is fully assembled and leads to T-cell activation by enabling interaction between the T-cell receptor (TCR) and human leukocyte antigen class II (HLA-II). We established a novel rosetting model by coculturing HLA-II–matched peripheral blood mononuclear cells with HL cell lines and showed IS formation with activation of rosetting T cells. HLA-II downregulation by class II transactivator knockout did not affect the extent of rosetting, but almost completely abrogated T-cell activation. Intriguingly, the level of CD58 expression correlated with the extent of rosette formation, and CD58 knockout or CD2 blockade reduced both rosette formation and T-cell activation. The extension of our findings to primary HL tissue by immunohistochemistry and proximity ligation assays showed interaction of CD2 with CD58 and of TCR-associated CD4 with HLA-II. In conclusion, T-cell rosetting in HL is established by formation of the IS, and activation of rosetting T cells critically depends on the interaction of both TCR-HLA-II and CD2-CD58.

scholarly journals AB0151 PRELIMINARY RESULTS SHOW AN INCREASED EXPRESSION OF COINHIBITORY RECEPTORS IN SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1376.2-1376
Author(s):  
M. Aspari ◽  
S. R. Greisen ◽  
M. Hvid ◽  
B. Deleuran ◽  
D. Abraham
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Systemic Sclerosis ◽  
T Cell ◽  
Healthy Volunteers ◽  
T Cell Activation ◽  
Cell Activation ◽  
Programmed Death ◽  
Programmed Death 1

Background:Recent studies suggest dysregulation in T cell activation in systemic sclerosis (SSc). Co-inhibitory-receptors (Co-IRs) such as TIM-3, PD-1 and LAG-3 play a crucial role in controlling excessive T cell activation and in maintaining immune homeostasis. Engagement of these receptors by their ligand’s limits cytokine production in response to TCR or activating NK receptor stimulation and hence limit tissue damage from excessive immune activation. However, chronically increased expression of multiple Co-IRs is a hallmark of immune exhaustion. We evaluate the role of these soluble Co-IRs in diffuse SSc (dcSSc).Objectives:Establish the role of CiR and their ligands in diffuse systemic sclerosis.Understand how immune regulatory mechanisms influence the development of fibrosis.Provide a better understanding of the disease and fibrosis in general.Methods:PBMC’s(Peripheral blood mononuclear cells) and dermal fibroblasts from SSc patients were isolated and investigated for markers of T cell inhibition. These cells were analysed using flow cytometry in a 10 colour panel. Cells were stained for PD1, TIM3, TIGIT, LAG3, CD3, CD8, CD4 and CD19 along with a Live/dead marker. Co-cultures of fibroblasts and PBMCs will be setup, and treated with various drugs that act on the Co-IRs.Results:The proportion of CD4+ T cells expressing PD1 were markedly increased in SSc patients compared to healthy volunteers and Rheumatoid Arthritis patients.There was increased expression of both TIGIT and TIM3 in the CD4+ T cells. (Figure 1)Similarly, the co-expression of these receptors on the CD4+ T cell population was elevated compared to healthy volunteers. (figure 2)Conclusion:Soluble co-inhibitors are differentially expressed in early dcSSc compared to healthy volunteers and other autoimmune diseases. Our preliminary data indicates that these co inhibitors could play an important role in unravelling the pathogenesis of systemic sclerosis. Inhibition or activation of these receptors through different treatment modalities can be utilized as a novel patient centric treatment strategy.References:[1]Fukasawa, T., Yoshizaki, A., Ebata, S., Nakamura, K., Saigusa, R., Miura, S., … Sato, S. (2017). Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic Sclerosis.Arthritis & Rheumatology,69(9), 1879–1890.[2]Greisen S, Rasmussen T, Stengaard-Pedersen K, Hetland M, Hørslev-Petersen K, Hvid M, et al. Increased soluble programmed death-1 (sPD-1) is associated with disease activity and radiographic progression in early rheumatoid arthritis. Scand J Rheumatol 2014; 43:101-8.[3]de Paoli, F., Nielsen, B., Rasmussen, F., Deleuran, B., & Søndergaard, K. (2014). Abatacept induces clinical improvement in patients with severe systemic sclerosis.Scandinavian Journal of Rheumatology,43(4), 342–345.[4]Kwon, B. (2010). Intervention with costimulatory pathways as a therapeutic approach for graft-versus-host disease.Experimental and Molecular Medicine. Nature Publishing Group.Acknowledgments:FOREUM: Foundation of Research in RheumatologyDisclosure of Interests:None declared

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