scholarly journals POS0593 THE REDUCTION OF RETINAL MICROVASCULAR ALTERATIONS AND THE DECREASE OF A POTENTIALLY RELATED T-CELL SUBSET IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS TREATED WITH ABATACEPT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 530.1-530
Author(s):  
S. Piantoni ◽  
F. Regola ◽  
S. Masneri ◽  
C. Nalli ◽  
C. Bazzani ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
T Cells ◽  
T Cell ◽  
Cell Number ◽  
Sectional Area ◽  
Microvascular Damage ◽  
Cross Sectional ◽  
Retinal Arterioles ◽  
Microvascular Alterations

Background:T-cells play a pivotal role in the pathogenesis of rheumatoid arthritis (RA) and in its cardiovascular (CV) comorbidities, acting at microvascular level [1]. Since small artery remodeling is the earliest form of target organ damage in hypertension, the evaluation of microvascular alterations might provide clinically useful information. The evaluation of retinal arterioles is a non-invasive technique to identify a precocious microvascular damage, which is related to an increase of the wall-to-lumen ratio (WLR) [2]. CD3+CD31+CXCR4+ T-cells may be involved in damaged endothelium repair and are increased in patients with morphological microvascular alterations [3]. In addition to its effect on disease activity, abatacept (ABA), a co-stimulator blocker which is approved for the treatment of RA, may have specific CV protective action, modulating the numbers of certain subtypes of lymphocytes [4].Objectives:To non-invasively investigate morphological characteristics of retinal arterioles and to evaluate CD3+CD31+CXCR4+T-cells in a cohort of RA patients treated with ABA.Methods:Eleven RA patients [median (25th-75thpercentile) age=58 (50-65) years, baseline C-reactive protein (CRP)-DAS28=4.4 (3.8-4.6), body mass index (BMI)=23.4 (21.6-25.6) kg/m2, rheumatoid factor (RF) positive:45%, anti-citrullinated peptide autoantibodies (ACPA) positive:73%] without known CV risk factors (arterial hypertension, diabetes, hypercholesterolemia, previous CV events, smoking) were evaluated by adaptive optics, a validated technique quantifying microvascular damage [5], before and every 6 months of therapy with ABA (T0, T6 and T12). Phenotypic analysis of peripheral blood T lymphocytes was made by flow-cytometry in 5 patients of the cohort at T0 and T6.Results:A progressive significant reduction of the WLR of retinal arterioles was observed [T0=0.28 (0.25-0.30), T6=0.27 (0.24-0.31), T12=0.23 (0.23-0.26); p T0 vs T6=0.4; p T6 vs T12=0.01; p T0 vs T12=0.01] (Figure 1), without significant variations in the other parameters [internal diameter: T0=94.4 (84.1-104.0), T6=94.8 (84.6-107.7), T12=99.2 (89.1-109.1) µm; external diameter: T0=125.8 (111.1-131.0), T6=122.4 (109.1-134.5), T12=125.6 (113.9-134.4) µm; wall thickness: T0=13.2 (12.2-14.4), T6=13.4 (11.7-14.4), T12=12.5 (11.6-13.0) µm; wall cross-sectional area: T0=4581.0 (3788.7-5263.7), T6=4563.3 (3788.5-5295.2), T12=4099.7 (3899.0-5145.7) µm2)]. In 5 patients evaluated also for T-cell immunophenotyping a negative correlation was observed between CD3+CD31+CXCR4+ T-cell number and the retinal wall thickness at baseline (R=0.871;p=0.05). After ABA therapy a trend for reduction of CD3+CD31+CXCR4+T-cells [19.0 (13.8-38.3) vs 12.4 (5.2-18.0) % of CD3+], was observed as well as of significant reduction of retinal wall cross-sectional area [5123.3 (4385.0-5470.3) vs 4852.3 (4118.3-5228.0) µm2;p=0.04].Conclusion:In a cohort of RA patients without known CV risk factors, a reduction in retinal microvascular alterations arterioles was demonstrated after treatment for 12 months with ABA. CD3+CD31+CXCR4+T-cell number was inversely related to the possible presence of subclinical CV involvement. These results may suggest the possibility of microvascular abnormalities regression induced by the immune system modulation.References:[1]Dessein PH, J Rheumatol 2005.[2]Rizzoni D, Am J Hypertens. 2018.[3]Hur J, Circulation 2007.[4]Kallikourdis M, Nat Commun 2017.[5]De Ciuceis C, J Hypertens 2018.Acknowledgements:Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduct.Figure 1.Disclosure of Interests:None declared

scholarly journals Early microvascular modifications in patients previously hospitalized for COVID-19: comparison with healthy individuals

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
P Malerba ◽  
C Agabiti Rosei ◽  
M Nardin ◽  
A Gaggero ◽  
G Chiarini ◽  
...  
Keyword(s):  
Adaptive Optics ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Healthy Individuals ◽  
Cross Sectional ◽  
Retinal Arterioles ◽  
Wide Range ◽  
Baseline Characteristics ◽  
Microvascular Alterations

Abstract Background SARS-CoV2 infection has been associated to a wide range of clinical scenarios, named COVID-19, ranging from acute respiratory distress syndrome to blood coagulation abnormalities and vascular manifestations related to hyper-inflammation. Recent focus has been addressed to study of microvascular alterations which may explain COVID-19 pathophysiology. Alterations in microvascular structure, identified as increased wall to lumen ratio (WLR) of retinal arterioles, have been extensively described in patients with cardiovascular diseases, such as hypertension or diabetes mellitus. Both inflammation and immune system dysregulation seem to play a role in the pathogenesis of these morphological changes. Purpose Aim of this study was to evaluate through Adaptive Optics microvascular differences of retinal arterioles between patients experienced COVID-19 and controls. Methods Patients were hospitalized between 28th February and 15th April at a Internal Medicine ward in a tertiary care hospital. All patients tested positive for a SARS-CoV-2 nasopharyngeal swab at admission and showed signs of pneumonia and respiratory insufficiency. Adaptive Optics, which allows a non-invasive evaluation of retinal arteriole structure, and blood chemistry exams were performed as part of follow up visits between 2 to 3 months after hospitalization. Baseline characteristics were collected through medical records. COVID-19 patients were compared to age- and sex-matched healthy subjects referred to our center between 2018 and 2019. Results A total of 80 patients were included in this study (of which 40 were COVID-19 patients). Apart from smoking habit, other baseline characteristics (sex, age, cardiovascular risk factors and main comorbidities) did not differ between the two groups. At follow up visit COVID-19 patients showed lower values for leukocytes (6.2 vs. 7.5x103/μL, p=0.015) and lymphocytes (1.9 vs. 2.8x103/μL, p=0.002). Creatinine values were higher in patients who suffered from COVID-19 (1.0 vs 0.8 mg/dl, p=0.004 – Figure 1, panel A). Adaptive Optics showed no differences in terms of internal lumen, wall thickness and WLR of retinal arterioles. However, the wall cross-sectional area (WCSA) was found to be higher in COVID-19 patients (p=0.039 – Figure 1, panel B). Hypertension significantly affected both WCSA and WLR between COVID-19 and healthy individuals, while diabetes only impacted on WLR (Figure 2). Conclusion Previous studies described the presence of leukopenia and lymphopenia during the acute phase of SARS-CoV2 infection. Our study demonstrates that these alterations persist several weeks after symptoms onset. Adaptive Optics showed microvascular alterations occurring in these patients: in particular, higher wall cross-sectional area of retinal arterioles were observed in patients after COVID-19 hospitalization, reflecting the complex pathogenic mechanisms which may explain the wide range of symptoms and clinical severity. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

scholarly journals Molecular remission at T cell level in patients with rheumatoid arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun Inamo ◽  
Katsuya Suzuki ◽  
Masaru Takeshita ◽  
Yasushi Kondo ◽  
Yuumi Okuzono ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Disease Control ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Principal Component ◽  
Cell Level ◽  
Molecular Remission ◽  
Signature Genes

AbstractWhile numerous disease-modifying anti-rheumatic drugs (DMARDs) have brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain, such as the small proportion of patients who achieve drug-free status. The aim of this study was to explore key molecules for remission at the T cell level, which are known to be deeply involved in RA pathogenesis, and investigate the disease course of patients who achieved molecular remission (MR). We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4+ T cells and CD8+ T cells from patients with RA using machine learning methods. In addition, we investigated the benefits of achieving MR on disease control. We identified 9 and 23 genes that were associated with clinical remission in CD4+ and CD8+ T cells, respectively. Principal component analysis (PCA) demonstrated that their expression profiling was similar to those in HCs. For the remission signature genes in CD4+ T cells, the PCA result was reproduced using a validation cohort, indicating the robustness of these genes. A trend toward better disease control was observed during 12 months of follow-up in patients treated with tocilizumab in deep MR compared with those in non-deep MR, although the difference was not significant. The current study will promote our understanding of the molecular mechanisms necessary to achieve deep remission during the management of RA.

scholarly journals POS0584 ULTRASONOGRAPHY OF THE MEDIAN NERVE IN PATIENTS WITH RHEUMATOID ARTHRITIS UNDER SUSPICION OF CARPAL TUNNEL SYNDROME

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 525.1-525
Author(s):  
S. Tsiami ◽  
E. Ntasiou ◽  
C. Krogias ◽  
R. Gold ◽  
J. Braun ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Carpal Tunnel Syndrome ◽  
Median Nerve ◽  
Carpal Tunnel ◽  
Nerve Conduction Velocity ◽  
Sectional Area ◽  
Cross Sectional ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Tunnel Syndrome

Background:Carpal tunnel syndrome (CTS) is the most common nerve compression syndrome and a common extra-articular manifestation of rheumatoid arthritis (RA). Different causes of CTS are known, among them inflammatory and non-inflammatory pathologies. Electroneurography (ENG) of the median nerve, the method of choice to diagnose CTS, measures impairment of nerve conduction velocity without explaining its underlying cause. However, because the electrical stimulation is often not well tolerated, ENG results may come out inconclusive. Using greyscale ultrasonography (GS-US) provides anatomic information including a structural representation of the carpal tunnel.Objectives:To investigate the performance of nerve GS-US in the diagnosis of CTS in patients with RA.Methods:Consecutive patients with active RA under suspicion of CTS presenting to a large rheumatologic center were included. Both hands were examined by an experienced neurologist including ENG and a GS-US (ML linear probe with 6-15 Hz) of the median nerve. An established grading system for ENG (1), and an established system for GS-US based on cut-offs for the nerve cross sectional area (CSA) [mild: 0,11-0,13cm2, moderate: 0,14-0,15 cm2, severe: > 0,15 cm2 CTS (2)] were used. In addition, the Boston Carpal Tunnel Syndrome Questionnaire (BCTSQ) was used to assess CTS symptoms (3).Results:Both hands of 58 patients with active RA (n=116) and clinical suspicion of CTS (in 38 cases bilaterally) were included. After clinical examination, CTS was suspicious in 96 hands (82.8%), and 59 of all hands had a final diagnosis of CTS (50.9%). Of the latter, 43 hands (72.9%) had a positive ENG and 16 (27.1%) a positive GS-US finding only, while 30 hands (50.8%) were positive in both examinations.There was a good correlation of the cross-sectional area (CSA) as well as the CSA-ratio to the ENG findings: the larger the CSA, the more severe was the CTS as assessed by ENG (Spearman’s rho=0.554; p<0.001). The more severe the GS-US findings of CTS were, the more definite were the distal motor latency (Spearman’s rho=0.554; p<0.001) and sensible nerve conduction velocity of the median nerve (Spearman’s rho=-0.5411; p<0.001).In the 46 hands positive in GS-US, tenosynovial hypertrophy of the flexor tendons was detected in 19 hands (41.3%), 7 of which (36.8%) also showed an additional cystic mass. In these 19 patients, clinical complains were more severely present than in patients with non-inflammatory CTS, as assessed by the BCTSQ with a total score of 68.8±13.4 vs. 59.3±13.7, respectively (p=0.007).Conclusion:In patients with active RA and clinical complains of CTS, ultrasound examinations provide additional information about inflammation which is helpful for a diagnosis of CTS. Thus, ENG and nerve GS-US should be used complementary for a diagnostic workup of CTS in RA patients with a suspicion of CTS. Power-Doppler may further improve the diagnostic performance of GS-US.References:[1]Padua L et al. Acta Neurol Scand 1997; 96:211–217[2]El Miedany et al., Rheumatology (Oxford). 2004 Jul; 43(7):887-895[3]Levine DW et al. J Bone Joint Surg Am 1993; 75: 1585-1592Figure 1.BCTSQ scores in patients with diagnosis of CTS and absence or presence of RA-related tenosynovial hypertrophyDisclosure of Interests:None declared

scholarly journals Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 245
Author(s):  
Daniil Shevyrev ◽  
Valeriy Tereshchenko ◽  
Elena Blinova ◽  
Nadezda Knauer ◽  
Ekaterina Pashkina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Homeostatic Proliferation ◽  
Suppressive Activity ◽  
Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

scholarly journals THU0046 A PIPELINE TO STUDY ANTIGEN-SPECIFIC CD4+ T CELLS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 235.1-236
Author(s):  
R. Kumar ◽  
N. Yoosuf ◽  
C. Gerstner ◽  
S. Turcinov ◽  
K. Chemin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Tenascin C ◽  
Tetramer Staining ◽  
Tcr Repertoire ◽  
Citrullinated Antigen

Background:Autoimmunity to citrullinated autoantigens forms a critical component of disease pathogenesis in rheumatoid arthritis (RA). Presence of anti-citrullinated protein antibodies (ACPAs) in patients has high diagnostic value. Recently, several citrullinated antigen specific CD4+T cells have been described. However, detailed studies of their T-cell receptor usage and in-vivo profile suffer from the disadvantage that these cells are present at very low frequencies. In this context, we here present a pipeline for TCR repertoire analysis of antigen-specific CD4+T cells from RA patients, including both citrulline and influenza (control) specificities using in-vitro peptide challenge induced-cell expansion.Objectives:To enable studies of the T cell repertoire of citrullinated antigen-specific CD4+T cells in rheumatoid arthritisMethods:Peripheral blood mononuclear cells (PBMCs) (n=7) and synovial fluid mononuclear cells (SFMCs) (n=5) from HLA-DR*0401-postive RA patients were cultured in the presence of citrullinated Tenascin C peptide cocktails or influenza peptides (positive control). Citrulline reactive cells were further supplemented with recombinant human IL-15 and IL-7 on day 2. All cultures were replenished with fresh medium on day 6 and rIL-2 was added every 2 days from then. Assessment of proportion of peptide-HLA-tetramer positive cells was performed using flow cytometry whereby individual antigen-specific CD4+T cells were sorted into 96-well plates containing cell lysis buffer, followed by PCR-based alpha/beta TCR sequencing. TCR sequencing data was demultiplexed and aligned for TCR gene usage using MiXCR. Some tetramer positive cells were sorted into complete medium containing human IL-2 and PHA for expansion of antigen-specific cells. Cells were supplemented with irradiated allogenic PBMCs (30 times number of antigen specific cells). Clones of antigen specific CD4+T cells were further subjected to tetramer staining to confirm expansion of cells.Results:As evidenced by increase in frequency of tetramer positive CD4+T cells, in vitro peptide stimulation resulted in expansion of both influenza specific (Fig. 1a) and citrullinated antigen specific (Fig. 1b) CD4+T cells. Polyclonal in-vitro expansion of tenascin C tetramer positive sorted cells followed by tetramer staining further confirmed antigen specificity and enrichment for antigen specific CD4+T cells after polyclonal stimulation (Fig.1c). TCR repertoire analysis in PB and SF dataset from the first patient showed clonal expansion of influenza specific cells in both sites. Synovial fluid had more diversity of expanding clones as compared to paired PB, with few expanded clones being shared among SF and PB. We observed a more diverse TCR repertoire in citrulline specific CD4+T cells. We also observed sharing of TCR alpha chains among different citrulline specific CD4+T cell clones.Fig. 1In-vitroexpansion of antigen specific CD4+T cells:Conclusion:This method provides a highly suitable approach for investigating TCR specificities of antigen specific CD4+T cells under conditions of low cell yields. Building on this dataset will allow us to assess specific features of TCR usage of autoreactive T cells in RA.PBMCs were cultured in presence of (a) influenza (HA, MP54) and (b) citrullinated tenascin peptides. The proportion of antigen specific CD4+T cells was assessed using HLA-class II tetramer staining. We observed an increase in frequency of (a) Infleunza specific cells (red dots in upper left and lower right quadrants) and (b) citrullinated tenascin C specific cells (red dots in lower right quadrant), at day 13 post culture as compared to day 3. (c) Sorting of citrullinated tenascin specific CD4+T cells, followed by PHA expansion resulted in visible increase in proportion of citrullinated tenascin specific CD4+T cells.Disclosure of Interests:Ravi kumar: None declared, Niyaz Yoosuf: None declared, Christina Gerstner: None declared, Sara Turcinov: None declared, Karine Chemin: None declared, Vivianne Malmström Grant/research support from: VM has had research grants from Janssen Pharmaceutica

scholarly journals Incidence and Risk Factors for Symptomatic Spinal Epidural Hematoma Following Posterior Thoracic Spinal Surgery in a Single Institute

2020 ◽  
pp. 219256822097914
Author(s):  
Longjie Wang ◽  
Hui Wang ◽  
Zhuoran Sun ◽  
Zhongqiang Chen ◽  
Chuiguo Sun ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cerebrospinal Fluid ◽  
Spinal Surgery ◽  
Cerebrospinal Fluid Leakage ◽  
Sectional Area ◽  
Kyphosis Angle ◽  
Cross Sectional ◽  
Thoracic Spinal ◽  
Local Kyphosis ◽  
Spinal Epidural

Study Design: Case-control study. Objectives: To investigate the incidence of symptomatic spinal epidural hematoma (SSEH) and recognize its risk factors in a cohort of patients undergoing posterior thoracic surgery in isolation. Methods: From January 2010 to December 2019, patients who developed SSEH after posterior thoracic surgery and underwent hematoma evacuation were enrolled. For each SSEH patient, 2 or 3 controls who did not develop SSEH and underwent the same procedures with similar complexity at the same section of the thoracic spine in the same period were collected. The preoperative and intraoperative factors, blood pressure-related factors and radiographic parameters were collected to identify possible risk factors by comparing between the 2 groups. Results: A total of 24 of 1612 patients (1.49%) were identified as having SSEH after thoracic spinal surgery. Compared to the control group (53 patients), SSEH patients had significant differences in the APTT (p = 0.028), INR (p = 0.009), ratio of previous spinal surgery (p = 0.012), ratio of cerebrospinal fluid leakage (p = 0.004), thoracic kyphosis (p<0.05), local kyphosis angle (p<0.05), epidural fat ratio at T7 (p = 0.003), occupying ratio of the cross-sectional area (p<0.05) and spinal epidural venous plexus grade (p<0.05). Multiple logistic regression analysis revealed 3 risk factors for SSEH: cerebrospinal fluid leakage, the local kyphosis angle (>8.77°) and the occupying ratio of the cross-sectional area (>49.58%). Conclusions: The incidence of SSEH was 1.49% in posterior thoracic spinal surgeries. Large local kyphosis angle (>8.77°), high occupying ratio of cross-sectional area (>49.58%) and cerebrospinal fluid leakage were identified as risk factors for SSEH.

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4550-4556 ◽  
Author(s):  
Frederique Ponchel ◽  
Ann W. Morgan ◽  
Sarah J. Bingham ◽  
Mark Quinn ◽  
Maya Buch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Large Population ◽  
Chronic Inflammatory Disease ◽  
T Cell Differentiation ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells

Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the synovium of uncertain pathogenesis. A number of phenotypic and functional T-cell defects have been described in RA, including abnormal clonal expansions and suppressed proliferative responses, which suggest a defect in T-cell differentiation. Here, we show that RA patients possess fewer naive CD4+ T cells than healthy controls. Furthermore, a smaller proportion of these cells contains a T-cell receptor excision circle (TREC). Patients with RA also have unusual populations of T cells. These include immature cells characterized as CD45RBbrightCD45RA+CD62L− by flow cytometry and a large population that coexpresses CD45RA and CD45RO. These cells are hyperresponsive to mitogen and TCR stimulation when compared to naive cells. Additionally, an unusual putative central memory subset expressing CD62L, but not CD45RA, appears in RA patients at the expense of more typical cells. Levels of C-reactive protein correlate inversely with the TREC content of naive T cells and positively with the sizes of naive and immature atypical T-cell subsets. These data suggest that inflammation drives proliferation of naive T cells in RA and encourages their differentiation into atypical, hyperresponsive progeny. TREC content of individual naive and atypical T-cell subsets suggests an ontogeny consistent with this hypothesis. These studies provide further evidence of a T-cell differentiation defect in RA, which could explain some of the well-characterized immunologic features of the disease.

scholarly journals Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Cécile Alanio ◽  
Francesco Nicoli ◽  
Philippe Sultanik ◽  
Tobias Flecken ◽  
Brieuc Perot ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Infection ◽  
Surface Expression ◽  
Cross Sectional Study ◽  
Negative Regulator ◽  
Tcr Signaling ◽  
Cell Repertoire ◽  
Cross Sectional ◽  
Chronic Hcv

Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8+ T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8+ T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8+ T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection.

scholarly journals Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Korawit Kanjana ◽  
Parawee Chevaisrakul ◽  
Ponpan Matangkasombut ◽  
Karan Paisooksantivatana ◽  
Putthapoom Lumjiaktase
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Inhibitory Activity ◽  
Clinical Remission ◽  
Positive Likelihood Ratio ◽  
High Specificity ◽  
Cell Types ◽  
Cross Sectional ◽  
Remission Status ◽  
Plasma Cytokines

AbstractImmune regulation status may indicate immunological remission in rheumatoid arthritis (RA). This cross-sectional study aimed to determine the Regulatory T cell (Treg) properties, together with 14 plasma cytokines levels between active RA and clinical remission patients. Peripheral blood (PB) Foxp3+ Treg was collected from RA patients for determination of Treg inhibitory activity using a co-culture system. Other PB T cell types and plasma cytokines were determined by flow-cytometry. The Treg results were analyzed according to the disease activity score-28 (DAS28). Then sensitivity and specificity were calculated for the indication of the remission status. The number and inhibitory activity of Treg are higher in the clinical remission as compared to the active RA (p value < 0.0001). Also, Treg: CD4+CD25+CD127+ cell ratio demonstrates the similar result (p value < 0.05). Treg inhibitory activity is inversely correlated with the DAS28. Specificity and positive likelihood ratio of inhibitory activity for indicating remission status are 92.31% (95% CI 63.97–99.81) and 11.14 (95% CI 1.67–74.14), respectively. Treg inhibitory activity is a promising prognostic marker and probably represents the immunological remission status in RA.

scholarly journals Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2227-2236 ◽  
Author(s):  
NA Kernan ◽  
C Bordignon ◽  
G Heller ◽  
I Cunningham ◽  
H Castro-Malaspina ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cells ◽  
T Cell ◽  
Human Leukocyte Antigen ◽  
Graft Failure ◽  
Human Leukocyte ◽  
Marrow Transplant ◽  
High Dose ◽  
Leukocyte Antigen ◽  
Major Factors

Abstract Risk factors for graft failure were analyzed in 122 recipients of an allogeneic T-cell-depleted human leukocyte antigen (HLA)-identical sibling marrow transplant as treatment for leukemia. In each case pretransplant immunosuppression included 1,375 to 1,500 cGy hyperfractionated total body irradiation and cyclophosphamide (60 mg/kg/d x 2). No patient received immunosuppression prosttransplant for graft-versus-host disease (GVHD) prophylaxis. Nineteen patients in this group experienced graft failure. The major factors associated with graft failure were transplants from male donors and the age of the patient (or donor). Among male recipients of male donor-derived grafts a low dose per kilogram of nucleated cells, progenitor cells (colony forming unit-GM) and T cells was also associated with graft failure. Additional irradiation to 1,500 cGy, high dose corticosteroids posttransplant, and additional peripheral blood donor T cells did not decrease the incidence of graft failure. In addition, type of leukemia, time from diagnosis to transplant, an intact spleen, or the presence of antidonor leukocyte antibodies did not correlate with graft failure. To ensure engraftment of secondary transplants, further immunosuppression was necessary but was poorly tolerated. However, engraftment and survival could be achieved with an immunosuppressive regimen in which antithymocyte globulin and high dose methylprednisolone were administered both before and after infusions of secondary partially T- cell-depleted marrow grafts.

Sign in / Sign up

Export Citation Format

Share Document