Plasma Indoleamine-2,3-Dioxygenase (IDO) is Increased in Drug-Naï ve Major Depressed Patients and Treatment with Sertraline and Ketoprofen Normalizes IDO in Association with Pro-Inflammatory and Immune- Regulatory Cytokines

2020 ◽  
Vol 19 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Ahmed Jasim Twayej ◽  
Arafat Hussein Al-Dujaili ◽  
Michael Maes
Keyword(s):  
Inflammatory Response ◽  
Clinical Efficacy ◽  
Transforming Growth Factor ◽  
Antidepressant Treatment ◽  
Regulatory System ◽  
Antiinflammatory Drug ◽  
Future Research ◽  
Indoleamine 2,3 Dioxygenase ◽  
Ifn Γ ◽  
Tgf Β1

Background: Major Depression Disorder (MDD) is accompanied by an immune response characterized by increased levels of inflammatory and immune-regulatory cytokines and stimulation of indoleamine-2,3-dioxygenase (IDO). There is also evidence that anti-inflammatory drugs may have clinical efficacy in MDD. Objective: This study examined a) IDO in association with interferon (IFN)-γ, Interleukin (IL)-4 and Transforming Growth Factor (TGF)-β1 in 140 drug-naïve MDD patients and 40 normal controls; and b) the effects of an eight-week treatment of sertraline with or without ketoprofen (a nonsteroidal antiinflammatory drug) on the same biomarkers in 44 MDD patients. Results: Baseline IDO, IFN-γ, TGF-β1 and IL-4 were significantly higher in MDD patients as compared with controls. Treatment with sertraline with or without ketoprofen significantly reduced the baseline levels of all biomarkers to levels which were in the normal range (IDO, TGF-β1, and IL-4) or still somewhat higher than in controls (IFN-γ). Ketoprofen add-on had a significantly greater effect on IDO as compared with placebo. The reductions in IDO, IL-4, and TGF-β1 during treatment were significantly associated with those in the BDI-II Conclusion: MDD is accompanied by activated immune-inflammatory pathways (including IDO) and the Compensatory Immune-Regulatory System (CIRS). The clinical efficacy of antidepressant treatment may be ascribed at least in part to decrements in IDO and the immune-inflammatory response. These treatments also significantly reduce the more beneficial properties of T helper-2 and T regulatory (Treg) subsets. Future research should develop immune treatments that target the immune-inflammatory response in MDD while enhancing the CIRS.

scholarly journals Ketoprofen as an Add-on Treatment to Sertraline for Drug-Naïve Major Depressed Patients: Normalization of Plasma Levels of Indoleamine-2,3-Dioxygenase in Association with Pro-Inflammatory and Immune Regulatory Cytokines

2018 ◽  
Author(s):  
Hussein Al-Hakeim ◽  
Ahmed Jasim Twayej ◽  
Arafat Hussein Al-Dujaili ◽  
Michael Maes
Keyword(s):  
Clinical Efficacy ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Serum Levels ◽  
Future Research ◽  
Control Group ◽  
Clinical Effects ◽  
Indoleamine 2,3 Dioxygenase ◽  
Anti Inflammatory ◽  
Normal Controls

Major Depression Disorder (MDD) is accompanied by an immune response characterized by increased levels of pro-inflammatory and immune-regulatory cytokines and cytokine-induced stimulation of indoleamine-2,3-dioxygenase (IDO). There is also some evidence that anti-inflammatory drugs may have a clinical efficacy in MDD.The aim of this study is to examine the clinical effects of an eight-week combinatorial treatment of ketoprofen (a nonsteroidal anti-inflammatory drug) combined or not with sertraline, on serum levels of IDO, interferon (IFN)-γ, interleukin (IL)-4 and transforming growth factor (TGF)-β1 in association with changes in the Beck-Depression Inventory-II (BDI-II). The study included 140 MDD patients and 40 normal controls. The pre-treatment serum levels of IDO, IFN-γ, TGF-β1 and IL-4 were significantly higher in MDD patients compared with the control group. Treatment with sertraline with or without ketoprofen significantly reduced the increased baseline production of all 4 biomarkers to levels which were similar as those of normal controls. Ketoprofen add-on had a significantly greater effect on IDO and BDI-II as compared with placebo. The reductions in IDO, IL-4 and TGF-β1 during treatment were significantly associated with those in the BDI-II.In conclusion, the clinical efficacy of both sertraline + ketoprofen may be ascribed at least in part to attenuated IDO levels and immune-inflammatory responses in MDD. Moreover, add-on treatment with ketoprofen may augment the efficacy of sertraline by attenuating IDO. However, these treatments may also significantly reduce the more beneficial properties of T helper-2 and T regulatory (Treg) immune subsets. Future research should develop immune treatments that target the immune-inflammatory response in MDD, while enhancing the compensatory immune-regulatory system (CIRS).

scholarly journals Yiqi Wenyang Fang ameliorates allergic rhinitis through inhibiting inflammatory response and promoting the expression of Foxp3

2016 ◽  
Vol 29 (4) ◽  
pp. 696-706 ◽  
Author(s):  
Jun Shi ◽  
Yu Liu ◽  
Shihai Yan ◽  
Daonan Yan
Keyword(s):  
Allergic Rhinitis ◽  
Inflammatory Response ◽  
Transforming Growth Factor ◽  
Treg Cells ◽  
Pcr Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Sprague Dawley ◽  
Model Control ◽  
Tgf Β1

Allergic rhinitis (AR) is an inflammatory disease with a hypersensitivity response to environmental stimulus. The aim of this study was to evaluate the effect of Yiqi Wenyang Fang (YWF) on AR and investigate the underlying mechanism. A total of 48 female Sprague-Dawley rats were randomly divided into six groups (normal control, model control, YWF at low dose, YWF at median dose, YWF at high dose, and loratadine). Rats were injected with antigen for sensitization. Then, rats in the YWF groups were treated with different dose of YWF for 28 days. Loratadine was used as a positive control. Number of sneezes, degree of runny nose, nasal rubbing movements, and tissue damage were scored. The protein and mRNA expression of Foxp3 were determined by western blot and real time-PCR analysis, respectively. Flow cytometry was used to detect the number of CD4+CD25+Foxp3+ Treg cells. The content of interleukin (IL)-10, transforming growth factor β1 (TGF-β1), IL-13, and IL-4 in the serum were detected by enzyme-linked immunosorbent assay (ELISA). Scores of symptoms were significantly reduced and nasal mucosa damage was alleviated after YWF administration. YWF increased the expression of Foxp3, IL-10, TGF-β1, and number of CD4+CD25+Foxp3+ Treg cells which were reduced by antigen injection. The expression levels of IL-13 and IL-4 were increased after antigen administration while decreased after YWF treatment. YWF may ameliorate AR through inhibiting inflammatory response and promoting Foxp3 expression.

scholarly journals Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

2020 ◽  
Vol 8 (B) ◽  
pp. 738-746
Author(s):  
Haryudi Aji Cahyono ◽  
Wisnu Barlianto ◽  
Dian Handayani ◽  
Handono Kalim
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Premature Atherosclerosis ◽  
Ifn Γ ◽  
Tgf Β1

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process. AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]). METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019). RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%). CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

scholarly journals microRNA-145-5p attenuates acute lung injury via targeting ETS2

2021 ◽  
Author(s):  
Liang Qiao ◽  
Rongxia Li ◽  
Shangang Hu ◽  
Yu Liu ◽  
Hongqiang Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Growth Factor ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Transforming Growth Factor ◽  
Recombinant Adenovirus ◽  
Transforming Growth Factor Β1 ◽  
Inflammatory Factors ◽  
Smad Pathway ◽  
Tgf Β1

Abstract Objective Previously, the protective effect of microRNA (miR)-145-5p has been discovered in acute lung injury (ALI). Thus, this study attempts to further discuss the mechanism of miR-145-5p in ALI through the downstream E26 transformation-specific proto-oncogene 2 (ETS2)/transforming growth factor β1 (TGF-β1)/Smad pathway. Methods A lipopolysaccharide (LPS)-induced rat ALI model was established. Recombinant adenovirus miR-145-5p and/or ETS2 overexpression plasmid was administrated into rats. Afterwards, pathological damage in the lung tissue, wet/dry (W/D) ratio, apoptosis and contents of serum inflammatory factors were observed. miR-145-5p, ETS2, TGF-β1, Smad2/3, phosphorylated Smad2/3 levels were measured in rats. Results miR-145-5p was down-regulated, ETS2 was up-regulated and TGF-β1/Smad pathway was activated in LPS-suffered rats. Overexpression of miR-145-5p inactivated the TGF-β1/Smad pathway and attenuated ALI, as reflected by relived pathological damage, and decreased W/D ratio, apoptosis and inflammatory response. Oppositely, loss of miR-145-5p or enhancement of ETS2 worsened ALI and activated the TGF-β1/Smad pathway. Moreover, elevation of ETS2 decreased miR-145-5p-mediated protection against ALI. Conclusion Evidently, miR-145-5p negatively regulates ETS2 expression and inactivates TGF-β1/Smad pathway to ameliorate ALI in rats.

scholarly journals Treatment of Experimental (Trinitrobenzene Sulfonic Acid) Colitis by Intranasal Administration of Transforming Growth Factor (Tgf)-β1 Plasmid

2000 ◽  
Vol 192 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Atsushi Kitani ◽  
Ivan J. Fuss ◽  
Kazuhiko Nakamura ◽  
Owen M. Schwartz ◽  
Takashi Usui ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sulfonic Acid ◽  
Transforming Growth Factor ◽  
Intraperitoneal Administration ◽  
Experimental Colitis ◽  
Inhibitory Effect ◽  
Transforming Growth Factor Β1 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Ifn Γ ◽  
Tgf Β1

In this study, we show that a single intranasal dose of a plasmid encoding active transforming growth factor β1 (pCMV-TGF-β1) prevents the development of T helper cell type 1 (Th1)-mediated experimental colitis induced by the haptenating reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid administration abrogates TNBS colitis after it has been established, whereas, in contrast, intraperitoneal administration of rTGF-β1 protein does not have this effect. Intranasal pCMV-TGF-β1 administration leads to the expression of TGF-β1 mRNA in the intestinal lamina propria and spleen for 2 wk, as well as the appearance of TGF-β1–producing T cells and macrophages in these tissues, and is not associated with the appearances of fibrosis. These cells cause marked suppression of interleukin (IL)-12 and interferon (IFN)-γ production and enhancement of IL-10 production; in addition, they inhibit IL-12 receptor β2 (IL-12Rβ2) chain expression. Coadministration of anti–IL-10 at the time of pCMV-TGF-β1 administration prevents the enhancement of IL-10 production and reverses the suppression of IL-12 but not IFN-γ secretion. However, anti–IL-10 leads to increased tumor necrosis factor α production, especially in established colitis. Taken together, these studies show that TGF-β1 inhibition of a Th1-mediated colitis is due to: (a) suppression of IL-12 secretion by IL-10 induction and (b) inhibition of IL-12 signaling via downregulation of IL-12Rβ2 chain expression. In addition, TGF-β1 may also have an inhibitory effect on IFN-γ transcription.

Evaluation of the immune response induced by DNA vaccines expressing MIF and MCD-1 genes ofTrichinella spiralisin BALB/c mice

2011 ◽  
Vol 86 (4) ◽  
pp. 430-439 ◽  
Author(s):  
F. Tang ◽  
L. Xu ◽  
R. Yan ◽  
X. Song ◽  
X. Li
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Transforming Growth Factor ◽  
Trichinella Spiralis ◽  
Challenge Infection ◽  
Specific Immunoglobulin ◽  
Ifn Γ ◽  
Antibody Levels ◽  
Phosphate Buffered Saline ◽  
Tgf Β1

AbstractPlasmids expressing macrophage migration inhibitory factor (MIF) ofTrichinella spiralis(TsMIF), multi-cystatin-like domain protein (MCD-1) ofT. spiralis(TsMCD-1), or co-expressingTsMIF andTsMCD-1 were constructed with a pVAX1 vector. Their ability to generate a protective immune response againstT. spiralisinfection was evaluated in BALB/c mice. Groups of mice were immunized twice at 2-week intervals with 100 μg of recombinant plasmids pVAX1-Tsmif, pVAX1-Tsmcd-1or pVAX1-Tsmif-Tsmcd-1. Control animals were immunized with phosphate-buffered saline (PBS) or blank vector plasmid. Specific antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, IgA, IgE) against the recombinant proteinTsMIF-TsMCD-1, serum cytokines (interferon (IFN)-γ, interleukin (IL)-4, IL-5, transforming growth factor (TGF)-β1 and IL-17) and CD4+/CD8+T cells were monitored. Challenge infection was performed 2 weeks following the second immunization and worm burden was assayed at 35 days post-challenge. Vaccination with pVAX1-Tsmifinduced moderate serum IFN-γ and increases of CD4+and CD8+T cells, but no specific immunoglobulin antibody response. Vaccination with pVAX1-Tsmcd-1induced a predominant Th1 antibody (IgG2a and IgG2b) response and strong levels of serum IFN-γ, and increases of CD4+T cells. Importantly, co-expression ofTsMIF andTsMCD-1 in DNA immunization produced more serum IFN-γ and markedly enhanced CD4+and CD8+T cells than the single DNA vaccine of the two genes. Challenge infection demonstrated that immunization with pVAX1-Tsmif-Tsmcd-1reduced worm burdens (by 23.17%;P < 0.05).

scholarly journals Transforming Growth Factor -β Level Might Be An Independent Factor Related to Occurrence of Chronic Hepatitis B

2021 ◽  
Author(s):  
Ming-hui Li ◽  
Yao Lu ◽  
Fang-fang Sun ◽  
Qi-qi Chen ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Growth Factor ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Alanine Aminotransferase ◽  
Transforming Growth Factor ◽  
Independent Factor ◽  
Alanine Aminotransferase Level ◽  
Ifn Γ ◽  
Tgf Β1

Abstract To investigate association between immune cell-related cytokines and development of chronic hepatitis B (CHB). Patients with chronic hepatitis B virus (HBV) infection in immune tolerance (IT, n=30) and hepatitis B envelope antigen (HBeAg) positive CHB (n=250) were enrolled in the study. HBV virus, serological indicators, and plasma cytokine levels were detected at the time of enrollment. The results showed that there were significant differences in median age of patients (27 vs. 31y), alanine aminotransferase level (ALT, 29.85 vs 234.70 U/L), alanine aminotransferase level (AST, 23.40 vs. 114.90 U/L), HBsAg level (4.79 vs. 3.88 log10 IU/ml), HBeAg (1606.36 vs. 862.47 S/CO) and HBV DNA load (8.17 vs 6.71 log10 IU/ml) between IT and CHB groups (all P<0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-γ (IFN-γ), interleukin- 17A (IL-17A) and transforming growth factor- beta (TGF-β1) in IT group were significantly higher than those in CHB group (FLT3-L: 41.62 vs. 27.47 pg/ml; IFN-γ: 42.48 vs. 33.18 pg/ml; IL-17A: 15.66 vs. 8.90 pg/ml; TGF-β1: 4921.50 vs. 2234 pg/ml. All P<0.01). The median values of IFN-a2, TGF-β3 and IL-10 levels in IT group were significantly lower than those in CHB group (IFN-α2: 15.24 vs. 35.78 pg/ml, P=0.000; TGF-β3: 131.69 vs. 162.61 pg/ml, P=0.025; IL-10: 5.02 vs. 7.9 pg/ml, P=0.012). The multivariate logistic regression analysis indicated that TGF-β 1 (OR=0.999, 95% CI 0.999-1.000, P<0.001) and TGF-β2 levels (OR=1.008, 95%CI 1.004-1.012, P <0.001) were significantly associated with the incidence of CHB. The results suggest that TGF-β level might be an independent factor related to the occurrence of CHB.

Sex Hormones, BDNF, Leptin, and TGF-β1 in Females With IBS: A Pilot Investigation

2020 ◽  
pp. 109980042094858
Author(s):  
Kristen R. Weaver ◽  
Christina M. Boulineaux ◽  
Jeffrey M. Robinson ◽  
Kierra Butler ◽  
Margaret M. Heitkemper ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Contraceptive Use ◽  
Transforming Growth Factor ◽  
Depression Scale ◽  
Symptom Assessment ◽  
Epidemiological Studies ◽  
Future Research ◽  
Enzyme Linked Immunosorbent Assay ◽  
Female Sex ◽  
Tgf Β1

Background: Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition predominantly affecting the female sex, and is characterized by brain-gut axis dysregulation. Relevance of hormones along the hypothalamic-pituitary gonadal axis and hypothalamic-pituitary adrenal axis to IBS symptomatology remain unclear, as does the significance of other modulators including brain derived neurotrophic factor (BDNF), leptin, and transforming growth factor βeta 1 (TGF-β1). Methods: Females with IBS were compared with female healthy controls (HC) on age, race, hormonal contraceptive use, body mass index, adrenocorticotropic hormone, cortisol, estradiol, follicular stimulating hormone, luteinizing hormone, progesterone, total cholesterol, Center for Epidemiological Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS). BDNF, leptin, and TGF-β1 were quantified using enzyme-linked immunosorbent assay. Descriptive statistics, non-parametric techniques, and regression analyses were performed. Results: Participants with IBS (n = 12) displayed higher estradiol ( p = .027) than did HC (n = 21). Direction of associations among study variables often differed between groups: BDNF and progesterone in HC (rs = .623) and in IBS (rs = −.723). The relationship between log (CES-D) and log (estradiol) varied by IBS status (interaction term p = 0.019). Discussion: Elevated estradiol in participants with IBS, and differential patterns of biological and psychological indices between groups, encourages further inquiry on the relevance of sex hormones, BDNF, leptin, and TGF-β1 to symptoms of IBS. Future research endeavors should conduct longitudinal quantification of sex hormones with subjective symptom assessment to facilitate insight on the pathophysiology and female sex bias in IBS.

P–417 A comparison of baseline and sequential changes of extended cytokine profile during implantation window between women who did and did not conceive after embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Zhao ◽  
T Zhang ◽  
X Guo ◽  
C C Wang ◽  
T C Li
Keyword(s):  
Embryo Transfer ◽  
Inflammatory Cytokine ◽  
Transforming Growth Factor ◽  
Cytokine Profile ◽  
Blastocyst Transfer ◽  
Implantation Failure ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Tgf Β1

Abstract Study question To compare the changing peripheral levels of inflammation-related cytokine profile during a 9-day period after blastocyst transfer between women who did and did not conceive. Summary answer:Successful implantation is associated with transient increase in serum pro-inflammatory cytokine profile followed by a switch to anti-inflammatory cytokine profile prior to confirmation of pregnancy.What is known already: Immunomodulation is thought to be important for the prevention of rejection of the implanting semi-allograft embryo and successful establishment of pregnancy. A successful pregnancy is characterized by a dominance of anti-inflammatory cytokine profile in the peripheral blood in the first and second trimesters of pregnancy. It is achieved by a complex interplay between various immune cells and cytokines at the fetal-maternal interface, among which the key-players are interleukine–10 (IL–10) and transforming growth factor-β1 (TGF-β1). The circulating inflammatory response in the first few days after embryo transfer to the pathophysiology of implantation failure remains unclear. Study design, size, duration: This prospective observational and longitudinal study on 47 women with infertility was performed in an in vitro fertilization unit from December 2018 to August 2019. The amounts of a range of cytokines was measured on serial blood samples obtained during a 9-day period after blastocyst transfer. Participants/materials, setting, methods Serial blood samples were obtained on the day of embryo transfer, and 3, 6, and 9 days afterward for measurement of serum interferon gamma (IFN-γ), tumor necrosis factor alpha, interleukin (IL)–2, IL–4, IL–10, IL–12, IL–13, IL–17, IL–18, and IL–22 using cytometric bead arrays; transforming growth factor beta 1 (TGF-β1) was measured using commercial enzyme-linked immunosorbent assay kits. Main results and the role of chance The cytokine profile was similar between the women who conceived and those who did not on the day of blastocyst transfer. In women who conceived, IFN-γ and IL–17 (pro-inflammatory cytokines) exhibited a transient and significant increase on day 3 after blastocyst transfer, which decreased to the baseline levels by day 6. Meanwhile, IL–10 (anti-inflammatory cytokine) was increased significantly on days 6 and 9, and TGF-β1 (anti-inflammatory cytokine) was increased significantly on day 9 after blastocyst transfer. In women who did not conceive, there was a more pronounced increase in IFN-γ and IL–17 (pro-inflammatory cytokines) on day 3, which was sustained on days 6 and 9 without a switch to an anti-inflammatory cytokine profile. Among women who conceived after blastocyst embryo transfer, there was a transient and modest increase in serum pro-inflammatory cytokine profile (IFN-γ and IL–17) 3 days after blastocyst transfer, which was followed by a switch to anti-inflammatory cytokine profile (increase IL–10 and TGF-β1) by 6 days after blastocyst transfer and the latter increase was sustained 9 days after blastocyst transfer, when pregnancy was confirmed. Limitations, reasons for caution This is an observational study on peripheral blood cytokine levels, so it is not possible to draw conclusions if the implantation failure is due primarily to failure of the embryo to elicit a trigger for the switch or failure of maternal response to a normal trigger released by the embryo. Wider implications of the findings: The characteristic change in peripheral cytokine profile during successful implantation, well before confirmation of pregnancy, may provide an opportunity to develop serum biomarkers to monitor implantation and to understand the mechanism of its failure, especially in women who experience recurrent implantation failure after IVF. Trial registration number Not applicable

scholarly journals Hepatitis C Virus (HCV)-Specific CD8+ Cells Produce Transforming Growth Factor β That Can Suppress HCV-Specific T-Cell Responses

2007 ◽  
Vol 81 (11) ◽  
pp. 5882-5892 ◽  
Author(s):  
Nadia Alatrakchi ◽  
Camilla S. Graham ◽  
Hans J. J. van der Vliet ◽  
Kenneth E. Sherman ◽  
Mark A. Exley ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C ◽  
T Cell ◽  
Transforming Growth Factor ◽  
T Cell Responses ◽  
Regulatory Cells ◽  
Cell Responses ◽  
Hiv Coinfection ◽  
Ifn Γ ◽  
Tgf Β1

ABSTRACT Hepatitis C virus (HCV)-specific T-cell responses are rarely detected in peripheral blood, especially in the presence of human immunodeficiency virus (HIV) coinfection. Based on recent evidence that T-regulatory cells may be increased in chronic HCV, we hypothesized that functional blockade of regulatory cells could raise HCV-specific responses and might be differentially regulated in the setting of HIV coinfection. Three groups of subjects were studied: HCV monoinfected, HCV-HIV coinfected, and healthy controls. Frequencies of peripheral T cells specific for peptides derived from HCV core, HIV type 1 p24, and recall antigens were analyzed by gamma interferon (IFN-γ) enzyme-linked immunospot assay. HCV-specific T-cell responses were very weak in groups with HCV and HCV-HIV infections. Addition of blocking antibodies against transforming growth factor β1 (TGF-β1), -2, and -3 and interleukin-10 specifically increased the HCV-specific T-cell responses in both infected groups; however, this increase was attenuated in the group with HCV-HIV coinfection compared to HCV infection alone. No increase in recall antigen- or HIV-specific responses was observed. Flow cytometric sorter analysis demonstrated that regulatory-associated cytokines were produced by HCV-specific CD3+CD8+CD25− cells. Enhancement of the IFN-γ effect was observed for both CD4 and CD8 T cells and was mediated primarily by TGF-β1, -2, and -3 neutralization. In conclusion, blockade of TGF-β secretion could enhance peripheral HCV-specific T-cell responses even in the presence of HIV coinfection.

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