Immunopotentiating Role of IFN-γ in Early and Late Stages of Type 1 CD8 Effector Cell-Mediated Tumor Rejection

2001 ◽  
Vol 98 (1) ◽  
pp. 70-84 ◽  
Author(s):  
Mark J. Dobrzanski ◽  
Joyce B. Reome ◽  
Richard W. Dutton
Keyword(s):  
Effector Cell ◽  
Tumor Rejection ◽  
Ifn Γ ◽  
Late Stages

scholarly journals MBD2 acts as a repressor to maintain the homeostasis of the Th1 program in type 1 diabetes by regulating the STAT1-IFN-γ axis

2021 ◽  
Author(s):  
Tiantian Yue ◽  
Fei Sun ◽  
Faxi Wang ◽  
Chunliang Yang ◽  
Jiahui Luo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Type 1 Diabetes ◽  
Adoptive Transfer ◽  
Nod Mice ◽  
Transcriptional Level ◽  
Clinical Settings ◽  
Cpg Dna ◽  
Ifn Γ

AbstractThe methyl-CpG-binding domain 2 (MBD2) interprets DNA methylome-encoded information through binding to the methylated CpG DNA, by which it regulates target gene expression at the transcriptional level. Although derailed DNA methylation has long been recognized to trigger or promote autoimmune responses in type 1 diabetes (T1D), the exact role of MBD2 in T1D pathogenesis, however, remains poorly defined. Herein, we generated an Mbd2 knockout model in the NOD background and found that Mbd2 deficiency exacerbated the development of spontaneous T1D in NOD mice. Adoptive transfer of Mbd2−/− CD4 T cells into NOD.scid mice further confirmed the observation. Mechanistically, Th1 stimulation rendered the Stat1 promoter to undergo a DNA methylation turnover featured by the changes of DNA methylation levels or patterns along with the induction of MBD2 expression, which then bound to the methylated CpG DNA within the Stat1 promoter, by which MBD2 maintains the homeostasis of Th1 program to prevent autoimmunity. As a result, ectopic MBD2 expression alleviated CD4 T cell diabetogenicity following their adoptive transfer into NOD.scid mice. Collectively, our data suggest that MBD2 could be a viable target to develop epigenetic-based therapeutics against T1D in clinical settings.

scholarly journals Role of TRAIL and IFN-γ in CD4+ T Cell-Dependent Tumor Rejection in the Anterior Chamber of the Eye

2003 ◽  
Vol 171 (6) ◽  
pp. 2789-2796 ◽  
Author(s):  
Shixuan Wang ◽  
Zita F. H. M. Boonman ◽  
Hao-Chuan Li ◽  
YuGuang He ◽  
Martine J. Jager ◽  
...  
Keyword(s):  
T Cell ◽  
Anterior Chamber ◽  
Tumor Rejection ◽  
Cd4 T Cell ◽  
Ifn Γ

Effect of prolonged exercise and carbohydrate ingestion on type 1 and type 2 T lymphocyte distribution and intracellular cytokine production in humans

2005 ◽  
Vol 98 (2) ◽  
pp. 565-571 ◽  
Author(s):  
G. I. Lancaster ◽  
Q. Khan ◽  
P. T. Drysdale ◽  
F. Wallace ◽  
A. E. Jeukendrup ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Cytokine Production ◽  
Stress Hormone ◽  
Induced Stress ◽  
Ifn Γ ◽  
Exercise Induced

The present study was undertaken to examine the role of the exercise-induced stress hormone response on the regulation of type 1 and type 2 T lymphocyte intracellular cytokine production. Subjects performed 2.5 h of cycling exercise at 65% maximal O2 uptake while ingesting a 6.4% carbohydrate (CHO) solution, 12.8% CHO solution, or a placebo. Peripheral whole blood samples were stimulated and stained for T lymphocyte surface antigens (CD4 and CD8). Cells were then permeabilized, stained for intracellular cytokines, and analyzed using flow cytometry. Exercise resulted in a decrease ( P < 0.05) in the number and percentage of IFN-γ positive CD4+ and CD8+ T lymphocytes. These stimulated cells produced less IFN-γ immediately postexercise ( P < 0.05) and 2-h postexercise ( P < 0.05) compared with preexercise. However, CHO ingestion, which attenuated the exercise-induced stress hormone response compared with placebo ( P < 0.05), prevented both the decrease in the number and percentage of IFN-γ-positive CD4+ and CD8+ T lymphocytes and the suppression of IFN-γ production from stimulated CD4+ and CD8+ T lymphocytes. There was no effect of exercise on the number of, or cytokine production from, IL-4-positive CD4+ or CD8+ T lymphocytes. These data provide support for the role of exercise-induced elevations in stress hormones in the regulation of type 1 T lymphocyte cytokine production and distribution.

scholarly journals OX40 costimulation turns off Foxp3+ Tregs

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2501-2510 ◽  
Author(s):  
Minh Diem Vu ◽  
Xiang Xiao ◽  
Wenda Gao ◽  
Nicolas Degauque ◽  
Ming Chen ◽  
...  
Keyword(s):  
Effector Cell ◽  
De Novo ◽  
Costimulatory Molecule ◽  
Negative Regulator ◽  
Clinical Implications ◽  
Effector Cells ◽  
T Effector Cells ◽  
Ifn Γ ◽  
Tnfr Superfamily

OX40 is a recently identified T-cell costimulatory molecule that belongs to the TNF/TNFR superfamily. OX40 can be expressed by both activated T effector cells and Foxp3+ Tregs. It is well known that OX40 delivers a potent costimulatory signal to T effector cells, but very little is known about the role of OX40 in regulating the suppressor properties of Foxp3+ Tregs and the de novo generation of new inducible Foxp3+ Tregs from T effector cells. In the present study, we found, by using a newly created foxp3gfp knockin model, that OX40 was dispensable for the genesis and suppressor functions of naturally arising CD4+Foxp3+ Tregs, but stimulating OX40 on the Foxp3+ Tregs abrogated their ability to suppress T effector cell proliferation, IFN-γ production, and T effector cell-mediated allograft rejection. OX40 costimulation did not significantly affect proliferation and survival of the naturally arising Foxp3+ Tregs, but profoundly inhibited Foxp3 gene expression. Importantly, OX40 costimulation to T effector cells prevented the induction of new inducible Foxp3+ Tregs from T effector cells. Our study identified OX40 as a key negative regulator of Foxp3+ Tregs and may have important clinical implications in models of transplantation and autoimmunity.

scholarly journals Overexpression of Type 1 and 2 Diacylglycerol Acyltransferase Genes (JcDGAT1 and JcDGAT2) Enhances Oil Production in the Woody Perennial Biofuel Plant Jatropha curcas

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 699
Author(s):  
Tian-Tian Zhang ◽  
Huiying He ◽  
Chuan-Jia Xu ◽  
Qiantang Fu ◽  
Yan-Bin Tao ◽  
...  
Keyword(s):  
Jatropha Curcas ◽  
Soluble Sugars ◽  
Oil Production ◽  
Dry Weight ◽  
Diacylglycerol Acyltransferase ◽  
Seed Kernel ◽  
Woody Perennial ◽  
Late Stages

Diacylglycerol acyltransferase (DGAT) is the only enzyme that catalyzes the acyl-CoA-dependent acylation of sn-1, 2-diacylglycerol (DAG) to form triacylglycerol (TAG). The two main types of DGAT enzymes in the woody perennial biofuel plant Jatropha curcas, JcDGAT1 and JcDGAT2, were previously characterized only in heterologous systems. In this study, we investigated the functions of JcDGAT1 and JcDGAT2 in J. curcas.JcDGAT1 and JcDGAT2 were found to be predominantly expressed during the late stages of J. curcas seed development, in which large amounts of oil accumulated. As expected, overexpression of JcDGAT1 or JcDGAT2 under the control of the CaMV35S promoter gave rise to an increase in seed kernel oil production, reaching a content of 53.7% and 55.7% of the seed kernel dry weight, respectively, which were respectively 25% and 29.6% higher than that of control plants. The increase in seed oil content was accompanied by decreases in the contents of protein and soluble sugars in the seeds. Simultaneously, there was a two- to four-fold higher leaf TAG content in transgenic plants than in control plants. Moreover, by analysis of the fatty acid (FA) profiles, we found that JcDGAT1 and JcDGAT2 had the same substrate specificity with preferences for C18:2 in seed TAGs, and C16:0, C18:0, and C18:1 in leaf TAGs. Therefore, our study confirms the important role of JcDGAT1 and JcDGAT2 in regulating oil production in J. curcas.

scholarly journals Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells

2021 ◽  
Vol 22 (23) ◽  
pp. 12988
Author(s):  
Zhengkang Luo ◽  
Sara Lundin ◽  
Mariela Mejia-Cordova ◽  
Imane Hassani ◽  
Martin Blixt ◽  
...  
Keyword(s):  
B Cells ◽  
Low Dose ◽  
Autoimmune Diabetes ◽  
Healthy Controls ◽  
Regulatory B Cells ◽  
Experimental Autoimmune Uveitis ◽  
Ifn Γ ◽  
Experimental Autoimmune

The anti-inflammatory role of regulatory B cells (Breg cells) has been associated with IL-35 based on studies of experimental autoimmune uveitis and encephalitis. The role of Breg cells and IL-35+ Breg cells for type 1 diabetes (T1D) remains to be investigated. We studied PBMCs from T1D subjects and healthy controls (HC) and found lowered proportions of Breg cells and IL-35+ Breg cells in T1D. To elucidate the role of Breg cells, the lymphoid organs of two mouse models of T1D were examined. Lower proportions of Breg cells and IL-35+ Breg cells were found in the animal models of T1D compared with control mice. In addition, the systemic administration of recombinant mouse IL-35 prevented hyperglycemia after multiple low dose streptozotocin (MLDSTZ) injections and increased the proportions of Breg cells and IL-35+ Breg cells. A higher proportion of IFN-γ+ cells among Breg cells were found in the PBMCs of the T1D subjects. In the MLDSTZ mice, IL-35 administration decreased the proportions of IFN-γ+ cells among the Breg cells. Our data illustrate that Breg cells may play an important role in the development of T1D and that IL-35 treatment prevents the development of hyperglycemia by maintaining the phenotype of the Breg cells under an experimental T1D condition.

Type 2 immune response associated with silicosis is not instrumental in the development of the disease

2007 ◽  
Vol 292 (1) ◽  
pp. L107-L113 ◽  
Author(s):  
Pierre Misson ◽  
Frank Brombacher ◽  
Monique Delos ◽  
Dominique Lison ◽  
Francois Huaux
Keyword(s):  
Immune Response ◽  
Lung Fibrosis ◽  
Receptor Expression ◽  
Fibrotic Disease ◽  
Pulmonary Response ◽  
Type 2 Immune Response ◽  
Ifn Γ

It has been proposed that the development of lung fibrosis is associated with a T helper type 2 response, mainly characterized by IL-4 and IL-13 production. We investigated the potential role of type 2 immune polarization in the silicotic process and examined the pulmonary response to silica particles in mice genetically deficient for IL-4. We found that IL-4−/− mice were not protected against the development of silicosis, suggesting that IL-4 is not essential for the development of this fibrotic disease. By evaluating the intensity of silica-induced lung fibrosis in mice deficient for IL-4 receptor α (IL-4Rα), we showed that the establishment of pulmonary fibrosis was independent of both IL-4 and IL-13. Strong impairment of the type 2 immune response (IgG1) in the lungs of IL-4−/− and IL-4Rα−/− mice did not affect the development of the disease. Measurement of IL-13α2 receptor expression and IgG2a, IL-12p70, and IFN-γ levels in silica-treated IL-4−/− and IL-4Rα−/− animals showed that the development of silicosis was not related to an IL-13 signaling pathway or a switch to a type 1 response in deficient animals. Our data clearly indicate that the type 2 immune response associated with silicosis in mice is not required for the development of this inflammatory and fibrotic disease.

scholarly journals Critical Role of Type 1 Cytokines in Controlling Initial Infection with Burkholderia mallei

2006 ◽  
Vol 74 (9) ◽  
pp. 5333-5340 ◽  
Author(s):  
Caroline A. Rowland ◽  
Ganjana Lertmemongkolchai ◽  
Alison Bancroft ◽  
Ashraful Haque ◽  
M. Stephen Lever ◽  
...  
Keyword(s):  
T Cells ◽  
Critical Role ◽  
Disease Model ◽  
Cell Mediated Immunity ◽  
Burkholderia Mallei ◽  
Monocyte Chemoattractant Protein 1 ◽  
Ifn Γ

ABSTRACT Burkholderia mallei is a gram-negative bacterium which causes the potentially fatal disease glanders in humans; however, there is little information concerning cell-mediated immunity to this pathogen. The role of gamma interferon (IFN-γ) during B. mallei infection was investigated using a disease model in which infected BALB/c mice normally die between 40 and 60 days postinfection. IFN-γ knockout mice infected with B. mallei died within 2 to 3 days after infection, and there was uncontrolled bacterial replication in several organs, demonstrating the essential role of IFN-γ in the innate immune response to this pathogen. Increased levels of IFN-γ, interleukin-6 (IL-6), and monocyte chemoattractant protein 1 were detected in the sera of immunocompetent mice in response to infection, and splenic mRNA expression of IFN-γ, IL-6, IL-12p35, and IL-27 was elevated 24 h postinfection. The effects of IL-18, IL-27, and IL-12 on stimulation of the rapid IFN-γ production were investigated in vitro by analyzing IFN-γ production in the presence of heat-killed B. mallei. IL-12 was essential for IFN-γ production in vitro; IL-18 was also involved in induction of IFN-γ, but IL-27 was not required for IFN-γ production in response to heat-killed B. mallei. The main cellular sources of IFN-γ were identified in vitro as NK cells, CD8+ T cells, and TCRγδ T cells. Our data show that B. mallei is susceptible to cell-mediated immune responses which promote expression of type 1 cytokines. This suggests that development of effective vaccines against glanders should target the production of IFN-γ.

scholarly journals Role of Gamma Interferon and Interleukin-4 in Host Defense against the Human Filarial Parasite Brugia malayi

2000 ◽  
Vol 68 (5) ◽  
pp. 3034-3035 ◽  
Author(s):  
Subash Babu ◽  
Lisa M. Ganley ◽  
Thomas R. Klei ◽  
Leonard D. Shultz ◽  
T. V. Rajan
Keyword(s):  
Host Defense ◽  
Brugia Malayi ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Ifn Γ ◽  
Canonical Type ◽  
Time Required

ABSTRACT We have investigated the roles of gamma interferon (IFN-γ) and interleukin-4 (IL-4) in host defense against Brugia malayi. Our data suggest that the lack of either IFN-γ or IL-4 prolongs the time required to achieve sterile immunity, suggesting that both canonical type 1 and type 2 responses are involved in the clearance of infection.

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