TH17 Pathway and Associated Pro-Inflammatory Cytokines Promote Immune Dysfunction in Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3517-3517
Author(s):  
Rao Prabhala ◽  
Dheeraj Pelluru ◽  
Paola Neri ◽  
Mariateresa Fulciniti ◽  
James J. Driscoll ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Function ◽  
Inflammatory Cytokines ◽  
Th17 Cells ◽  
Cell Subset ◽  
Immune Dysfunction ◽  
T Cell Subsets ◽  
Cytokine Network ◽  
High Level ◽  
Pro Inflammatory Cytokines

Abstract Multiple myeloma (MM) is associated with significant immune dysfunction. Although various mechanisms mediating immune dysregulation in MM have been studied, its molecular and cellular basis is ill defined. IL-6, TGF-β and IL-1β have been implicated in this process, but their mechanism of effects on immune function have not been studied in MM. Together, IL-6 and TGF-β enhance the generation of TH17 cells, important in the development of immunity and auto-immunity. Additionally, TH17 cells are differentiated by number of inflammatory cytokines including, IL-21, IL-22, IL-23, and IL-27. Therefore, we evaluated the immune dysfunction and the role of TH17 cells and associated pro-inflammatory cytokines in myeloma. We have previously characterized that the production of TH1 mediated cytokines including IFN-γ following anti-CD3-mediated activation is significantly lower in myeloma PBMC compared to normal PBMC. We hypothesize that this may be regulated via skewing the immune system towards TH17 pathway. We observed that TH17 cells, measured by intra-cellular flow cytometry, are significantly increased in number in myeloma (16.9%) and MGUS (6.2%) compared to normal (3.3%). Furthermore, we analysed supporting pro-inflammatory cytokine network for the generation of TH17 cells in myeloma, which may be responsible for the observed TH17 skewing of T cell subsets. Sera from MGUS (n=12) and myeloma (n=17) patients were evaluated for the presence of these pro-inflammatory cytokines compared with normal sera (n=6) using ELISA. We observed significant increase in serum IL-21, IL-22 and IL-23 in MGUS (373 pg/ml, 14 pg/ml and 147 pg/ml respectively; p<0.05) and myeloma (296 pg/ml, 12 pg/ml and 215 pg/ml respectively; p<0.05) compared with normal (63 pg/ml, 1.5 pg/ml and 39 pg/ml respectively). In addition, we also observed that the myeloma PBMC stimulated in the presence of IL-6 and TGF-β, both of the cytokines present at a high level in myeloma, induced significant IL-23 production compared with normal. Importantly, IL-23 levels were 10 fold higher in myeloma BM samples compared with matching blood samples. These results indicate that the cytokines from myeloma BM microenvironment may be responsible for the observed T cell subset abnormality by favouring TH17 cells via IL-23/IL-21 production. These cytokines thus may be targets to modulate immune responses in myeloma to enhance immune function and devise effective vaccination strategies in the future.

scholarly journals THU0039 DECIPHERING DISEASE-RELEVANT T CELL SUBSETS IN RHEUMATOID ARTHRITIS IDENTIFIES A NOVEL CELLULAR SUBSET OF PATHOGENETIC IMPORTANCE IN THERAPEUTIC RESISTANCE.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 232.1-233
Author(s):  
M. Nyirenda ◽  
I. Mcinnes ◽  
C. Goodyear
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Inflammatory Cytokines ◽  
Regulatory T Cell ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Healthy Controls ◽  
T Cell Subset ◽  
Pro Inflammatory Cytokines

Background:Aberrant T cell responses are key in driving autoimmunity and are commonly associated with rheumatoid arthritis (RA). Unravelling pathways of importance in therapeutic partial response and failure is of critical importance, as this will potentially provide new insights into key drivers of immune-mediated pathogenesis.Objectives:To delineate disease-relevant T cell subsets in RA and assess their potential to act as cellular markers amenable to precision medicine approaches, particularly in the context of therapeutic partial or non-response.Methods:FACS-based immunophenotyping and ex-vivo functional response profiles of CD4+CD161+CCR2+CCR5+T cells were performed in peripheral blood mononuclear cells (PBMC) obtained from patients with RA and healthy controls, using previously characterised methodologies. RA patients fulfilled the 2010 ACR/EULAR criteria for RA. All samples were obtained after written consent, with the appropriate ethical approvals in place.Results:RA patients harboured a higher frequency of CCR2+CCR5+cells within the CD4+CD161+T cell compartment compared with healthy controls. In RA patients this T cell subset had a higher proportion of cells that secrete pro-inflammatory cytokines such as IL-17A, GM-CSF, IFN-γ, and TNF. Importantly, the CD4+CD161+CCR2+CCR5+T cell subset was significantly increased in DMARD non-responders compared to both responders and healthy controls. Moreover, in DMARD non-responders, these cells had a propensity to express increased proportions of pro-inflammatory cytokines. Notably, there was also a significant increase in the ratio of effector: regulatory T cell (Teff: Treg) compared to both responders and healthy controls. In addition, the CD4+CD161+CCR2+CCR5+T cell subset was less responsive to suppression by Tregs. In further support of a role for this T cell population in disease pathogenesis, the frequency of CD4+CD161+CCR2+CCR5+T cells significantly correlated with disease activity, as measured by the DAS28 (R2= 0.65; p = 0.003; n=11).Conclusion:Combined, our findings suggest that the CD4+CD161+CCR2+CCR5+T cell subset represents a substantially abnormal T cell subset in RA, exhibiting exaggerated pro-inflammatory responses, numerical abundance relative to Tregs, and resistant to regulation by Tregs. The CD4+CD161+CCR2+CCR5+T cell subset appears to be a marker of therapeutic response status in RA, via its contribution to disease pathology and highlights this subset as a potential therapeutic target in RA.References:[1]McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis.N Engl J Med. 2011;365(23):2205-19.[2]Mexhitaj I, Nyirenda MH, Li R, O’Mahony J, Rezk A, Rozenberg A,et al. Abnormal effector and regulatory T cell subsets in paediatric-onset multiple sclerosis.Brain. 2019;142(3):617-32.[3]Cosmi L, Cimaz R, Maggi L, Santarlasci V, Capone M, Borriello F,et al. Evidence of the transient nature of the Th17 phenotype of CD4+CD161+T cells in the synovial fluid of patients with juvenile idiopathic arthritis.Arthritis Rheum. 2011;63(8):2504-15.Disclosure of Interests:Mukanthu Nyirenda: None declared, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Carl Goodyear: None declared

scholarly journals CD4+ T-Cell Plasticity in Non-Infectious Retinal Inflammatory Disease

2021 ◽  
Vol 22 (17) ◽  
pp. 9584
Author(s):  
Yi-Hsing Chen ◽  
Sue Lightman ◽  
Virginia L. Calder
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Dual Function ◽  
Interleukin 17 ◽  
Th1 Cells

Non-infectious uveitis (NIU) is a potentially sight-threatening disease. Effector CD4+ T cells, especially interferon-γ-(IFNγ) producing Th1 cells and interleukin-17-(IL-17) producing Th17 cells, are the major immunopathogenic cells, as demonstrated by adoptive transfer of disease in a model of experimental autoimmune uveitis (EAU). CD4+FoxP3+CD25+ regulatory T cells (Tregs) were known to suppress function of effector CD4+ T cells and contribute to resolution of disease. It has been recently reported that some CD4+ T-cell subsets demonstrate shared phenotypes with another CD4+ T-cell subset, offering the potential for dual function. For example, Th17/Th1 (co-expressing IFNγ and IL-17) cells and Th17/Treg (co-expressing IL-17 and FoxP3) cells have been identified in NIU and EAU. In this review, we have investigated the evidence as to whether these ‘plastic CD4+ T cells’ are functionally active in uveitis. We conclude that Th17/Th1 cells are generated locally, are resistant to the immunosuppressive effects of steroids, and contribute to early development of EAU. Th17/Treg cells produce IL-17, not IL-10, and act similar to Th17 cells. These cells were considered pathogenic in uveitis. Future studies are needed to better clarify their function, and in the future, these cell subsets may in need to be taken into consideration for designing treatment strategies for disease.

Understanding the Immunomodulatory Effect of Mesenchymal Stem Cell Infused In Transplanted Patients with Steroid-Refractory GvHD

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2306-2306 ◽  
Author(s):  
Erica Dander ◽  
Giovanna Lucchini ◽  
Paola Vinci ◽  
Martino Introna ◽  
Sonia Bonanomi ◽  
...  
Keyword(s):  
T Cell ◽  
Inflammatory Cytokines ◽  
Conflicts Of Interest ◽  
Plasma Concentrations ◽  
Cell Subset ◽  
Third Party ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
The Mean ◽  
Steroid Refractory

Abstract Abstract 2306 In the last few years the usage of third party mesenchymal stem cells (MSC) as therapy for steroid-refractory Graft versus Host Disease (GvHD) is constantly increasing and holds big promises. Nevertheless, at our knowledge, studies on MSC efficacy have been scarcely corroborated by biological analysis of patient response to cell infusion. Here, we report the immunological monitoring of 8 patients (7 male, 1 female; aged 4 to 33 years), with steroid-refractory GvHD (grade II to III), who received MSCs, between August 2009 and June 2010. GvHD presented as acute in 6 cases and chronic in 2 cases. In 5 cases GvHD occurred as a single organ pathology (2 skin, 2 gut, 1 liver), while in 3 cases GvHD had multi-organ involvement (1 liver and oral mucosa, 1 skin and oral/ocular mucosa, 1 skin, gut and liver). All patients received 2 to 3 MSC infusions from third party donors aiming at 1 × 106/kg recipient body weight MSCs for each infusion. After MSC therapy, 2 patients showed complete response, 3 patients showed partial response, whereas 3 patients did not respond to MSC infusion. To better comprehend the immunomodulatory effects of MSC infusions, we studied GvHD plasmatic markers, inflammatory cytokines and CD4+ T-cell subsets circulating in the peripheral blood (PB) of enrolled patients before MSC infusion and at day 7, 14 and 28 after cell therapy. In accordance with clinical observations, in patients responding to MSC infusions, we observed a dramatic decrease of three validated GvHD plasmatic markers TNFRI, IL2Rα and elafin (Paczesny S et al. Blood 2009) to the mean levels of Healthy Donors (HD). In particular, at day 28 after therapy, TNFRI and IL2Rα levels decreased of 2 times (range=1.9-2.4 and range=1.4-2.8, respectively) and elafin levels decreased of 2.5 times (range=1.7-3.6). Partially responding patients showed a transient decrease of TNFRI, IL2Rα and elafin levels, while non responding patients showed stable or even increasing levels of all analysed markers. Moreover, we investigated the effect of MSC infusion on lymphocyte counts. We demonstrated that patients responding to MSC infusion, oppositely to non responders, strongly decreased total and CD4+ lymphocyte counts in the PB (mean total T-cell Fold Decrease (FD)=11.85, range=1.3-116; mean CD4+ T-cell FD=12, range=1.5-116). Interestingly, after MSC infusion, CD4+ T-cell subsets changed significantly: Tregs increased and Th1 and Th17 populations decreased, and a new CD4+ cell subset balance was observed starting from day 7 after therapy. In particular, the mean FD of Th1/Treg ratio was 4.1 (range=4-4.2) and the mean FD of Th17/Treg ratio was 4.7 (range=3.3-6). Correspondingly, patient symptoms also gradually improved, suggesting an association between GvHD clinical course and CD4+ T-cell imbalance, reverted by MSCs in responding patients. In partially responding patients Th1/Treg and Th17/Treg showed a transient decreased and even slightly increased in the case of non responding patients. In accordance with the decrease of Th1 CD4+ T cells in the PB of patients responding to MSC infusion, we observed a valuable decrease of IFNγ plasma concentrations (mean FD=48, range=30-65 in complete responders), which reached the levels typical of HD. In summary, despite its limited size, the present study suggests that MSCs, upon infusion, are able to convert an inflammatory environment to a more physiological one, both at a cellular level, promoting the expansion of circulating Tregs, and at a molecular level, diminishing inflammatory cytokines. Further studies on a larger group of patients, clarifying the mechanisms of action used in vivo by MSC to tune ongoing allo-reactions, will be fundamental to provide the rationale for improving current clinical trials. Disclosures: No relevant conflicts of interest to declare.

Lesions of thymus and decreased percentages of the peripheral blood T-cell subsets in chickens fed on diets excess in selenium

2011 ◽  
Vol 30 (12) ◽  
pp. 1972-1978 ◽  
Author(s):  
Xi Peng ◽  
Hengmin Cui ◽  
Yun Cui ◽  
Junliang Deng ◽  
Zhicai Zuo ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Function ◽  
Peripheral Blood ◽  
Morphological Changes ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Control Group ◽  
Cellular Immune Function ◽  
Group 5 ◽  
Cellular Immune

Selenium is an essential trace element possessing immune-stimulatory properties. The purpose of this 42-day study was to investigate the effects of excess dietary selenium on cellular immune function by determining morphological changes of thymus and peripheral blood T-cell subset. Three hundred 1-day-old avian broilers were fed on a basic diet (0.2 mg/kg selenium) or the same diet amended to contain 1, 5, 10, 15 mg/kg selenium supplied as sodium selenite ( n = 60/group). Pathological lesions were progressed with the dietary Se level increased. Grossly, the volume of thymus was decreased. Histopathologically, lymphopenia and congestion were observed. Ultrastructurally, mitochondria injury was observed. In comparison with that of control group, 5, 10 and 15 mg/kg dietary Se decreased the percentage of CD3+, CD3+CD4+ and CD3+CD8+ T cells of the peripheral blood, as measured by flow cytometry. The results showed that excess selenium (more than 5 mg/kg) intake could cause lesions of thymus and decrease of T-cell subsets. The cellular immune function was finally impaired in broilers.

Evidence for Associations Between Th1/Th17 “Hybrid” Phenotype and Altered Lipometabolism in Very Severe Graves Orbitopathy

2020 ◽  
Vol 105 (6) ◽  
pp. 1851-1867 ◽  
Author(s):  
Sijie Fang ◽  
Shuo Zhang ◽  
Yazhuo Huang ◽  
Yu Wu ◽  
Yi Lu ◽  
...  
Keyword(s):  
T Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
T Cell Subsets ◽  
Th1 Cell ◽  
Effector T Cell ◽  
Cell Lineages ◽  
Graves Orbitopathy ◽  
Ifn Γ

Abstract Purpose The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. Methods Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. Results In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-γt (RORγt) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced interferon-γ (IFN-γ). Increased IFN-γ–producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-γ–producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. Conclusions Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.

scholarly journals AB0827 SERUM NESPHATIN-1 IN PATHOGENESIS RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1437.2-1438
Author(s):  
T. Kvlividze ◽  
V. Polyakov ◽  
В. Zavodovsky ◽  
Y. Polyakova ◽  
L. Seewordova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Serum ◽  
Inflammatory Cytokines ◽  
Inflammatory Markers ◽  
Healthy People ◽  
Healthy Individuals ◽  
Markers Of Inflammation ◽  
High Level ◽  
Pro Inflammatory Cytokines

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared

scholarly journals AB0103 THE AMBIGUOUS ROLE OF TISSUE CYTOKINES IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1350.1-1351
Author(s):  
O. Korolik ◽  
В. Zavodovsky ◽  
E. Papichev ◽  
Y. Polyakova ◽  
S. L ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
High Activity ◽  
Inflammatory Cytokines ◽  
Stage Iii ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Fetuin A ◽  
High Level ◽  
Extraarticular Manifestations ◽  
Pro Inflammatory Cytokines

Background:Cytokines stimulate the inflammatory response in the synovial membrane with rheumatoid arthritis (RA), initiate apoptosis of chondrocytes, activation of osteoclasts. The progression of comorbid diseases is also associated with the influence of cytokines. At the same time, anti-inflammatory cytokines are produced in various tissues. Their role in the pathogenesis of RA and its complications is ambiguous.Adiponectin (A) and Fetuin A (FA) are classified as negative acute phase proteins. Their concentration decreases with an increase in the level of pro-inflammatory cytokines: TNF-α, IL-1 and IL-6. Molecules A and FA, regardless of various factors and from each other, have similar effects in relation to pro-inflammatory cytokines, lipid and carbohydrate metabolism.Visfatin (V) and Nesfatin-1 (N-1) are pro-inflammatory adipokines. B is produced by cells of the mononuclear phagocytic system and connective tissue. N-1 - is produced by the cells of the intermediate and medulla oblongata and by the cells of the gastric mucosa.Objectives:to study the correlation of B, H-1, A and FA with the severity of inflammation in RAMethods:60 patients with RA and 30 healthy individuals were examined. The level of cytokines was determined by an indirect enzyme-linked immunosorbent assay using commercial test systems (Bio Vendor, cat No. RD195023100, Bio Vendor Human Fetuin-A, RaiBiotech, cat No. EIA-VIS-1, RaiBiotech, cat No. EIA-NESF). All patients underwent a full examination. Diagnosed with 2010 EULAR / ACR recommendations.Results:A decreased level of A (less than 0.8 μg/ml) was detected in 15 patients (25%), F-A (less than 653.55 μg/ml) in 16 (27%), a high level of V (more than 39 ng/ml) - in 55 (91%), N-1 (more than 37.95 ng/ml) - in 36 (60%), which is significantly more often than in healthy individuals. No significant difference in the levels of determined adipokines was found depending on the gender and body weight of patients with RA. The level of cytokines in RA is associated with high activity according to DAS 28, positivity by Anti-CCP, extraarticular manifestations of RA. The greatest correlation with extraarticular manifestations is with cutaneous and cerebral vasculitis. The levels of FA and N-1 also correlated with more pronounced radiological changes (X-ray stage III). FA circulating inhibitor of ectopic calcification. N-1 level is positively correlated with systolic blood pressure.Conclusion:A low level of A and FA, a high level of V and N-1 is characteristic of RA with the presence of high activity and positivity in the RF and Anti-CCP. An increased level of B is determined by more than 90% of patients, which indicates its high pro-inflammatory activity. The level of F and N-1 is also associated with the degree of damage to bone tissue (stage III, a lot of erosion). A positive correlation of level V and N-1, negative A and FA with the severity of inflammation in RA confirms the involvement of these proteins in the pathogenesis. A high level of A and V increases the risk of developing cardiovascular diseases and their complications, the effect of N-1 and FA is being studied. The effect of cytokines on osteoclasts and osteoblasts in RA is ambiguousReferences:[1]Visfatin and Rheumatoid Arthritis: Pathogenetic Implications and Clinical Utility. Polyakova Y. Curr Rheumatol Rev.2019[2]Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Kvlividze T. Klinicheskaya Laboratornaya Diagnostika.2019; 64 (1):53-56 (in Russ)[3]Fetuin-A. Novel hepatokine in rheumatoid arthritis laboratory diagnostics. Papichev E. Klinicheskaya Laboratornaya Diagnostika.2018; 63 (12):756-760 (in Russ)Disclosure of Interests:None declared

scholarly journals Long-Term Depletion of Naive T Cells in Patients Treated for Hodgkin's Disease

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3662-3672 ◽  
Author(s):  
Nobukazu Watanabe ◽  
Stephen C. De Rosa ◽  
Anthony Cmelak ◽  
Richard Hoppe ◽  
Leonore A. Herzenberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Cell Counts

Abstract We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8αα homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4−, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.

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