CD4+CD25- effector T cells from healthy controls and MS patients do not differ in mRNA expression of IFN-γ, IL-2, and TNF-α

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
A Hug ◽  
J Haas ◽  
A Viehöver ◽  
B Fritz ◽  
B Storch-Hagenlocher ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Effector T Cells ◽  
Healthy Controls ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals Early Response of CD8+ T Cells in COVID-19 Patients

2021 ◽  
Vol 11 (12) ◽  
pp. 1291
Author(s):  
Deni Ramljak ◽  
Martina Vukoja ◽  
Marina Curlin ◽  
Katarina Vukojevic ◽  
Maja Barbaric ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Mrna Expression ◽  
Cd8 T Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Effector Memory ◽  
Healthy Controls ◽  
Ifn Γ

Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes (p = 0.007), CD3+ (p = 0.05), and CD8+ T cells (p = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) (p = 0.06) and effector memory 4 (EM4) (p < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 (p = 0.05) and lower mRNA expression of FASL (p = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 (p < 0.001) and IFN-γ (p < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK (p < 0.01) and FASL (p < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease.

scholarly journals Circulating cytokines and lymphocyte subsets in patients who have recovered from COVID-19

2020 ◽  
Author(s):  
Hasi Chaolu ◽  
Xinri Zhang ◽  
Xin Li ◽  
Xin Li ◽  
Dongyan Li
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Subsets ◽  
Healthy Controls ◽  
Tnf Α ◽  
Ifn Γ ◽  
Circulating Cytokines

To investigate the immune status of people who previously had COVID-19 infections, we recruited patients 2 weeks post-recovery and analyzed circulating cytokines and lymphocyte subsets. We measured levels of total lymphocytes, CD4+ T cells, CD8+ T cells, CD19+ B cells, CD56+ NK cells, and the serum concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most post-recovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8 + T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells(51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%) and IL-17 (97.06%). Compared to healthy controls, 2-week post-recovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17. Among post-recovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, post-recovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system has gradually recovered following COVID-19 infection; however, the sustained hyper-inflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

Identification of Previously Uncharacterized Delta 4-Positive Inflammatory Plasmacytoid Dendritic Cells That Play Important Roles in Eliciting Graft-Versus-Host Disease in Mice

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 337-337 ◽  
Author(s):  
Kazuhiro Mochizuki ◽  
Fang Xie ◽  
Shan He ◽  
Qing Tong ◽  
Yongnian Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Effector T Cells ◽  
Activated T Cells ◽  
Graft Versus Host ◽  
Notch Receptors ◽  
Tnf Α ◽  
Donor T Cells ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract Abstract 337 Graft-versus-host disease (GVHD) remains a major barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Host antigen-presenting cells (APCs) are known to be essential for presenting alloantigens to activate donor T cells to become effector cells mediating GVHD after allo-HSCT. However, APCs are heterogeneous populations. The identity of APC subset(s) that directs effector differentiation of alloantigen-activated T cells and by which mechanism this effect may be achieved remain largely unknown. The Notch signaling pathway controls cell proliferation, differentiation and survival. Upon interaction with Notch ligands of the δ-like family (Dll1, Dll3 and Dll4) and Jagged family (J1, J2), Notch receptors (Notch 1, 2, 3, and 4) are cleaved by γ-secretase and translocate into the nucleus to modify gene transcription. We have recently demonstrated that activation of Notch receptors in donor T cells is critical to the production of alloreactive effector T cells producing multiple inflammatory cytokines (e.g., IFN-γ, TNF-α and IL-17) during GVH reaction (Blood 2011). Building on these findings, we hypothesized that: 1) Notch ligand(s) derived from APCs may be important for directing effector differentiation of alloantigen-activated T cells, and 2) the expression of Notch ligand(s) may differentiate the capability of APCs to prime GVH responses. Using mouse models of GVHD, here we report the identification of previously uncharacterized Dll4-positive (Dll4+) inflammatory plasmacytoid dendritic cells (i-pDCs) and their roles in eliciting allogeneic T-cell responses. Host-derived Dll4+ i-pDCs occurred in the spleen of allo-HSCT recipients one day after transplantation, peaked by three days and declined by seven days. In contrast, host-derived inflammatory conventional DCs (i-cDCs) were Dll4-negative (Dll4−) and rapidly diminished by three days after transplantation. Notably, donor-derived DCs which occurred seven days after HSCT did not express Dll4. In vitro mixed lymphocyte-reaction (MLR) assay showed that these host-derived Dll4+ i-pDCs induced approximately 2.5-fold and 7-fold more IFN-γ- and IL-17-producing effector T cells than Dll4− i-cDCs, respectively. Addition of neutralizing antibody specific to Dll4 to the MLR cultures markedly reduced the production of IFN-γ and IL-17 in donor T cells stimulated by host Dll4+ i-pDCs, but had minimal impact on donor T cells cultured in the presence of Dll4− i-cDCs. These results suggest that Dll4+ i-pDCs may play important roles in directing effector differentiation of alloantigen-activated T cells. Further characterization of biological properties of Dll4+ i-pDCs revealed that as compared to unstimulated host pDCs at steady state conditions, Dll4+ i-pDCs expressed higher levels of antigen-presenting and costimulatory molecules, upregulated other Notch ligands (e.g.,J1 and J2) on their surface and produced more Ifnb and Il23. Notably, Dll4+ i-pDCs were mainly located in the spleen and intestine of mice receiving allogeneic HSCT. In vivo administration of Dll4 antibody reduced donor alloreactive effector T cell producing IFN-γ, IL-17 and TNF-α in GVHD target organs (in particular of the intestine), leading to reduction of GVHD and significantly improved survival of mice after allogeneic HSCT. Furthermore, adoptive transfer of in vitro generated Dll4+ i-pDCs caused severe GVHD in MHC-II-deficient mice (in which host DCs are incapable to elicit GVHD). Our findings identify that Dll4+ i-pDCs may represent a previously uncharacterized inflammatory APC population developed during GVH reaction. These Dll4+ i-pDCs and their-derived Dll4 are critical for directing differentiation of alloreactive effector T cells and may be beneficial therapeutic targets for modulating GVHD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Circulating Cytokines and Lymphocyte Subsets in Patients Who Have Recovered from COVID-19

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Hasichaolu ◽  
Xinri Zhang ◽  
Xin Li ◽  
Xin Li ◽  
Dongyan Li
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Subsets ◽  
Healthy Controls ◽  
Cell Counts ◽  
Tnf Α ◽  
Ifn Γ

To investigate the immune status of people who previously had COVID-19 infections, we recruited two-week postrecovery patients and analyzed circulating cytokine and lymphocyte subsets. We measured levels of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells and the serum concentrations of interleukin- (IL-) 1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most postrecovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8+ T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells (51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%), and IL-17 (97.06%). Compared to healthy controls, two-week postrecovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17. Among postrecovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells were positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, postrecovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system gradually recovers following COVID-19 infection; however, the sustained hyperinflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

scholarly journals Kinetics of the Immune Response Profile in Guinea Pigs after Vaccination with Mycobacterium bovis BCG and Infection with Mycobacterium tuberculosis

2009 ◽  
Vol 77 (11) ◽  
pp. 4837-4846 ◽  
Author(s):  
Ajay Grover ◽  
Jennifer Taylor ◽  
JoLynn Troudt ◽  
Andrew Keyser ◽  
Kimberly Arnett ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Mycobacterium Bovis ◽  
T Cell Activation ◽  
Guinea Pigs ◽  
Cell Activation ◽  
Activated T Cells ◽  
Bcg Vaccination ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT The guinea pig model of tuberculosis is used extensively in assessing novel vaccines, since Mycobacterium bovis BCG vaccination effectively prolongs survival after low-dose aerosol infection with virulent M. tuberculosis. To better understand how BCG extends time to death after pulmonary infection with M. tuberculosis, we examined cytokine responses postvaccination and recruitment of activated T cells and cytokine response postinfection. At 10 weeks postvaccination, splenic gamma interferon (IFN-γ) mRNA was significantly elevated compared to the levels at 5 weeks in ex vivo stimulation assays. At 15, 40, 60, and 120 days postinfection, T-cell activation (CD4+ CD62Llow and CD8+ CD62Llow) and mRNA expression of IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-10, IL-12, and eomesodermin were assessed. Our data show that at day 40, BCG-vaccinated guinea pigs had significantly increased levels of IFN-γ mRNA expression but decreased TNF-α mRNA expression in their lungs compared to the levels in nonvaccinated animals. At day 120, a time when nonvaccinated guinea pigs succumbed to infection, low levels of IFN-γ mRNA were observed even though there were increasing levels of IL-1, IL-12, and IL-10, and the numbers of activated T cells did not differ from those in BCG-vaccinated animals. BCG vaccination conferred the advantage of recruiting greater numbers of CD4+ CD62Llow T cells at day 40, although the numbers of CD8+ CD62Llow T cells were not elevated compared to the numbers in nonvaccinated animals. Our data suggest that day 40 postinfection may be a pivotal time point in determining vaccine efficacy and prolonged survival and that BCG promotes the capacity of T cells in the lungs to respond to infection.

scholarly journals Cytomegalovirus Infection- and Age-Dependent Changes in Human CD8+ T-Cell Cytokine Expression Patterns

2010 ◽  
Vol 17 (6) ◽  
pp. 986-992 ◽  
Author(s):  
Benjamin Faist ◽  
Bernhard Fleischer ◽  
Marc Jacobsen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Expression Patterns ◽  
Cytokine Expression ◽  
Effector T Cells ◽  
Study Group ◽  
Elderly Individuals ◽  
Tnf Α ◽  
Age Dependent ◽  
Ifn Γ

ABSTRACT T cells are strongly affected by immune aging, a phenomenon that leads to increased susceptibility to infections and decreased vaccination efficacy in elderly individuals. Cytomegalovirus (CMV) infection induces vigorous T-cell immune responses in humans and is thought to be a driving force of immune aging. In the present study we analyzed CMV-induced quantitative and qualitative differences in the cytokine-expressing T-cell repertoire from individuals of different age groups after in vitro stimulation. The CMV pp65 peptide pool and the superantigen Staphylococcus enterotoxin B (SEB) induced higher proportions of CD8+ effector T cells expressing gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor in the oldest study group, while only SEB induced increased responses in the middle-aged study group. Notably, CMV-specific multiple cytokine expression patterns revealed higher proportions of IFN-γ- and TNF-α-coexpressing CD8+ T cells exclusively in the oldest study group. These qualitative differences were absent in SEB-induced CD8+ effector T cells, although quantitative differences were detected. We report age-dependent qualitative changes in CMV-specific CD8+ T-cell cytokine patterns which are biocandidate markers of immune exhaustion in elderly individuals.

Effect of All-transretinoic Acid on Th17 and T Regulatory Cell Subsets in Patients with Ankylosing Spondylitis

2013 ◽  
Vol 40 (4) ◽  
pp. 476-483 ◽  
Author(s):  
Katayoon Bidad ◽  
Eisa Salehi ◽  
Ahmadreza Jamshidi ◽  
Ali Akbar Saboor-Yaraghi ◽  
Mona Oraei ◽  
...  
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
Cd4 T Cells ◽  
T Regulatory Cells ◽  
Interleukin 10 ◽  
Orphan Receptor ◽  
Healthy Controls ◽  
T Regulatory Cell ◽  
Tnf Α ◽  
Ifn Γ

Objective.We compared Th17 and T regulatory cells in patients with ankylosing spondylitis (AS) and in healthy controls. The effect of all-transretinoic acid (ATRA) was studied on cultured CD4+ T cells of patients with AS compared to controls.Methods.Eighteen patients with AS and 18 age- and sex-matched healthy controls were included. CD4+ T cells were separated and cultured in conditions of anti-CD3 and anti-CD28 stimulation with and without ATRA. Intracellular and secreted cytokines, transcription factors, and gene expression were evaluated after 72 h.Results.The frequency of CD4+IL-17+ T cells was significantly higher in patients with AS compared to controls, and ATRA could significantly decrease it. The frequency of forkhead box protein 3 (FOXP3)+ retinoic acid-related orphan receptor γt (RORγt) negative T-bet negative CD4+ cells was significantly lower in cases compared to controls. Intracellular and secreted interferon-γ (IFN-γ) was not significantly different between cases and controls. ATRA significantly increased intracellular IFN-γ in cases but not in controls. Tumor necrosis factor-α (TNF-α) secretion was significantly higher and interleukin 10 secretion was significantly lower in culture supernatant of cases compared to controls. ATRA could significantly decrease TNF-α secretion in cases.Conclusion.Our findings favor a pathogenic role for Th17 cells in AS. Th1 cells did not seem to contribute in the pathogenesis of this disease. The effect of ATRA as an immunomodulator on deviated immune cells was associated with decreased inflammatory markers. This association could be a reason for a clinical trial of ATRA in patients with AS.

scholarly journals The Characteristics of Natural Killer Cells and T Cells Vary With the Natural History of Chronic Hepatitis B in Children

2021 ◽  
Vol 9 ◽  
Author(s):  
Yingzhi Zhou ◽  
Yi He ◽  
Yunan Chang ◽  
Xiaorong Peng ◽  
Ruiqiu Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Immune Status ◽  
Healthy Controls ◽  
Tnf Α ◽  
Treatment Naïve ◽  
Ifn Γ

Background and Aims: The immune status of children with chronic hepatitis B (CHB) in different phases is still unclear. The aim of this study was to investigate the phenotype and cytokine-producing ability of natural killer (NK) and T cells and to better understand the immune characteristics of children with different phases of CHB.Methods: Treatment-naive children with CHB were divided into groups with different clinical phases of CHB. Fresh peripheral blood drawn from hepatitis B virus (HBV)-infected and healthy children was processed to perform flow cytometric analysis.Results: A total of 112 treatment-naive children with CHB and 16 comparable healthy controls were included in this study. The expression of HLA-DR on NK cells and CD38 on T cells were upregulated, especially in the IA phase, in children with CHB compared with healthy controls. The ability of circulating NK cells instead of CD8+ T cells to produce IFN-γ in children with CHB was slightly increased, but TNF-α production seemed to be decreased compared with that in healthy controls. The expression of some activation markers varied among children with different phases of CHB, especially the higher CD38 expression found on T cells in the IA phase. Regression analysis revealed that IFN-γ and TNF-α production by NK cells and CD8+ T cells seemed to have positive correlations with ALT elevation and an activated status of NK cells or T cells.Conclusion: NK cells and T cells tended to be phenotypically activated (especially in the IA phase) in children with CHB compared with healthy controls. However, their cytokine-producing function was not obviously elevated, especially IFN-γ production by CD8+ T cells. More studies investigating the mechanism and observing the longitudinal changes in the immune status in children with CHB are needed.

scholarly journals Cytokine mRNA expression in intestinal tissue of interleukin-2 deficient mice with bowel inflammation

Gut ◽  
1997 ◽  
Vol 41 (6) ◽  
pp. 793-800 ◽  
Author(s):  
I B Autenrieth ◽  
N Bucheler ◽  
E Bohn ◽  
G Heinze ◽  
I Horak
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Interleukin 2 ◽  
Cytokine Mrna ◽  
Colon Tissue ◽  
Intestinal Tissue ◽  
Tnf Α ◽  
Ifn Γ ◽  
Deficient Mice ◽  
Tgf Β1

Background—Mice deficient in interleukin-2 (IL-2) develop inflammatory bowel disease resembling ulcerative colitis in humans. Recent studies provided evidence that αβ T cells, particularly CD4 T cells, rather than B cells, are involved in the pathogenesis of bowel inflammation of IL-2 deficient mice.Aim—To analyse the pattern of expression of cytokine mRNA in intestinal tissue of normal and IL-2 deficient mice.Methods—Expression of β-actin, IL-1α, IL-1β, IL-6, IL-10, tumour necrosis factor α (TNF-α), interferon γ (IFN-γ) and transforming growth factor β1 (TGF-β1) mRNA was analysed in colon and small intestinal tissue of both IL-2 deficient (IL-2−/−) mice and normal (wild type) litter mates (IL-2+/+) at different ages by using qualitative, as well as semiquantitative, competitive reverse transcription polymerase chain reaction (RT-PCR). Results were correlated with the phase of progression of the disease, as determined by histology.Results—IL-2−/− mice had expressed low levels of IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ mRNA in the colon by 1.5 weeks of age. In advance of the development of histologically and clinically detectable bowel inflammation, expression of IL-1α, IL-1β, IL-6, TNF-α, IFN-γ, and IL-10, but not TGF-β1, mRNA increased in the colon of IL-2 deficient mice. In contrast, IL-2+/+ mice expressed TGF-β1 mRNA in colon tissue at 13 and 23 weeks of age, but not IL-1α, IL-1β, IL-6, TNF-α, IL-10, or IFN-γ mRNA. Levels of expression of cytokine mRNA in tissue from the small intestine were comparable in IL-2−/− and IL-2+/+ mice.Conclusions—Bowel inflammation in IL-2 deficient mice is preceded by an increase in IL-1α, IL-1β, TNF-α, and IFN-γ mRNA expression in colon tissue. Low levels of TGF-β1, but high levels of IL-1α, IL-1β, IL-6, TNF-α, IFN-γ, and IL-10 mRNA expression correlate with the manifestation of severe colitis, and suggest that T cells and macrophages are involved in bowel inflammation of IL-2 deficient mice.

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