Suppression of effector. Medical search. Frequent questions

Our findings suggest that FOXP3 governs a distinct transcriptional program in early-stage effector Tcons that maintains RICD resistance via CD48-dependent protective autophagy and p53 suppression. (nih.gov)
Furthermore, EAE protection was accompanied by sex- and genotype-specific suppression of proinflammatory transcriptional programs in CD4 T effector cells, yet not CD4 regulatory T cells, according to the study. (ajmc.com)
Cis-regulatory analysis of these integrated datasets enabled the identification of 28 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. (biorxiv.org)
Thus, our findings identify AgRP neuron-expressed IRF3 as a key transcriptional effector of the hunger-suppressing effects of leptin. (biorxiv.org)

Ionic immune suppression within the tumour microenvironment limits T cell effector function. (wikipedia.org)
and (iii) the dramatic reductions to lymphocyte numbers and function 1-2 h after exercise reflects a transient and time-dependent redistribution of immune cells to peripheral tissues, resulting in a heightened state of immune surveillance and immune regulation, as opposed to immune suppression. (frontiersin.org)
We have additionally identified multiple mechanisms of immune suppression that prevent the development of an endogenous effector T cell response. (hhs.gov)

A tumor cell has many ways to block tumor suppression mechanisms," she said. (cancer.gov)
tumor suppression activity. (cancer.gov)
Mechanistic studies revealed that this progression was mediated by suppressed TNFα levels, both locally and systemically, resulting in reduced expression of tumor endothelial adhesion molecules, particularly intercellular adhesion molecule-1 (ICAM-1) and a subsequent decrease in the number of activated and effector CD8 + T cells in the tumor. (aacrjournals.org)
As T cell metabolism dictates effector function, it is now apparent that the effect of cancer cell metabolism on the tumor microenvironment (TME) may impair anti-tumor immunity, and these new hallmarks of cancer are therefore inextricably linked. (elifesciences.org)
Activated GITR plays a role in directing the antitumor immune response by activating tumor-antigen-specific T effector cells, and abrogating the suppression induced by inappropriately activated T regulatory cells. (biopharminternational.com)

Finally, we transferred the disaggregated PtoDC3000 effector arsenal into Pseudomonas fluorescens and show that their cooperative action was sufficient to convert this rhizosphere-inhabiting beneficial bacterium into a phyllosphere pathogen. (nature.com)
Fig. 4: Effectors are sufficient for converting a beneficial strain into a pathogen. (nature.com)
Resistance is triggered by pathogen-delivered transcription activator-like effectors (TALEs) independent of their ability to activate transcription and is suppressed by truncated variants called truncTALEs, common among Asian strains. (uea.ac.uk)
This could one day allow for the engineering of bacteria with improved pathogen suppression capabilities useful for antibacterial and antifungal applications", John Whitney says. (mpg.de)

We disaggregated the 36 type III effectors of the phytopathogenic bacterium Pseudomonas syringae strain PtoDC3000 into a 'metaclone' of 36 coisogenic strains, each carrying a single effector in an effectorless background. (nature.com)
Groups led by Stefan Raunser of the Max Planck Institute for Molecular Physiology in Dortmund, Germany, and John Whitney of McMaster University in Canada have now jointly elucidated the high-resolution 3D structure of such an effector from Pseudomonas protegens using cryo-electron microscopy. (mpg.de)
3D structure of the Pseudomonas protegens RhsA effector. (mpg.de)

Critical factors in the differentiation of effector Th cells during inflammatory bowel disease (IBD). (frontiersin.org)
T cells must substantially increase nutrient uptake to mount a proper immune response and failure to obtain sufficient nutrients or engage the appropriate metabolic pathways can alter or prevent effector T cell differentiation and function. (elifesciences.org)
It is designed to expand the population of CD8+CD28+ central/effector memory T cells. (urologytimes.com)
In this way, it complements sunitinib-induced suppression of regulatory T cells and myeloid-derived suppressor cells. (urologytimes.com)
The mechanisms of action by which RTX kills FL cells include complement-dependent cytotoxicity (CDC) ( 3 ), antibody-dependent cellular cytotoxicity (ADCC) ( 4 , 5 )-herein referred to as 'effector function' mechanisms-as well as CD20 signaling effects ( 6 ). (spandidos-publications.com)
A comparative analysis of gene expression arrays from antigen-specific CD4(+) T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg-selective expression of LAG-3, a CD4-related molecule that binds MHC class II. (nih.gov)
Natural CD4(+)CD25(+) Tregs express LAG-3 upon activation, which is significantly enhanced in the presence of effector cells, whereas CD4(+)CD25(+) Tregs from LAG-3(-/-) mice exhibit reduced regulatory activity. (nih.gov)
Lastly, ectopic expression of LAG-3 on CD4(+) T cells significantly reduces their proliferative capacity and confers on them suppressor activity toward effector T cells. (nih.gov)
Recent studies indicate that memory T lymphocytes contain distinct populations of central memory (T CM cells) and effector memory (T EM ) cells characterized by distinct homing capacity and effector function. (scielo.br)
In this review, we have discussed the status and roles of various immune effector cells ( e.g ., dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC. (wjgnet.com)
The researchers observed decreased expression of proinflammatory genes with high Vit D in female CD4 T effector cells, which demonstrates the key role of MHC class II genes, interferon gamma, and Th1 cell-mediated neuroinflammation. (ajmc.com)
Many are similar to those seen in normal ageing, but they occur at an earlier age than normal.22 Persistent abnormalities include low CD4:CD8 ratio, low naive:memory cell ratio, expansion of CD28- effector T cells, reduced T cell repertoire, and reduced responsiveness to vaccines. (natap.org)
This work provides insight into how immune cells are sustained during infection, when the demand for immune effector cells is dramatically increased. (texaschildrens.org)
Thus, N-809 can potentially stimulate effector immune cells through IL-15 and block immunosuppressive PD-L1. (bmj.com)
This joint (Frankfurt/Mainz, Dresden, Essen, Heidelberg) translational immunotherapy project aims to combine NK cells as effector cells with universal epitope-specific CAR (UniCAR) with tunable activity. (unimedizin-mainz.de)

Metabotropic GABA B receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. (springer.com)

Rapid proliferation and acquisition of effector function are demanding processes that require precise metabolic re-wiring. (elifesciences.org)

One of the many bacterial weapons in this inevitable battle is the type VI secretion system (T6SS), which transports toxic effectors into enemies. (mpg.de)

Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. (biorxiv.org)

The 3D structure of one of these toxic proteins, the bacterial RhsA effector, has now been solved by the team of Stefan Raunser along with the team of John Whitney. (mpg.de)

To understand the spatial relationship of GABA B receptors with two key effector ion channels, the G protein-gated inwardly rectifying K + (GIRK/Kir3) channel and the voltage-dependent Ca 2+ channel, biochemical and immunohistochemical approaches were performed. (springer.com)
The effector protein, called RhsA, has a toxic component that sits unlocked and ready to fire in a molecular cocoon sealed by a cork-like structure. (mpg.de)
The scientists have shown that the effector protein itself cleaves the seal and the toxin from the rest of the protein, thereby unlocking the deadly weapon. (mpg.de)

They were able to reveal how effectors are transported inside the cell, how they are loaded on the poison dart and how the dart is then delivered into the host cell. (mpg.de)
They conclude that although armed with highly distinct effector functions, there are many parallels between the T cell and B cell components of the immune response and their conversion into memory. (scielo.br)
We are interested in the ways that such short term hematopoietic stem cell responses may ultimately contribute to syndromes of bone marrow dysfunction that are related to infection or inflammation, such as bone marrow suppression following tuberculosis and HIV/AIDS or acquired aplastic anemia as a result of EBV infection. (texaschildrens.org)
HAG Effector Evolution in Pyricularia Species and Plant Cell Death Suppression by HAG4 . (bvsalud.org)

The immune system has persistent defects even after years of treatment mediated viral suppression. (natap.org)
Most patients who take medication achieve durable and perhaps lifelong viral suppression, so the classic AIDS related conditions are becoming less common. (natap.org)

Although virulence is typically attributed to single pathogenic strains, here we investigated whether effectors secreted by a population of non-virulent strains could function as public goods to enable the emergence of collective virulence. (nature.com)
These observations suggest that suppression of Xo1-function by truncTALEs occurs through direct or indirect physical interaction. (uea.ac.uk)

Vigot and Batini 1997 ), the spatial relationship of GABA B and their effector ion channels in various subcellular compartments of central neurons remains mostly unknown. (springer.com)

They further suggest that effector coimmunoprecipitation may be effective for identifying or characterizing other resistance genes. (uea.ac.uk)

Evolution and Regulation of a Large Effector Family of Pyricularia oryzae . (bvsalud.org)

These data provide a better framework for understanding the different roles played by GABA B receptors and their effector ion channels in the cerebellar network. (springer.com)

Antibodies to LAG-3 inhibit suppression by induced Tregs both in vitro and in vivo. (nih.gov)

Each coisogenic strain was individually unfit, but the metaclone was collectively as virulent as the wild-type strain on Arabidopsis thaliana , suggesting that effectors can drive the emergence of cooperation-based virulence through their public action. (nature.com)

The scientists found that the RhsA effector consists of three connecting pieces: the toxic weapon itself, a cocoon surrounding it, and a cork-like plug which seals the toxin encapsulating cocoon entirely. (mpg.de)

Model showing arming of the effector (blue) and the poison dart (green). (mpg.de)

L-fucose did not trigger tumor suppression in immune-deficient mouse melanoma models, indicating the immune system's requirement for L-fucose-triggered suppression. (aacrjournals.org)
Immunodepletion of CD4+ or CD8+ T cells during L-fucose treatment revealed that CD4+ T cells are crucial for tumor suppression. (aacrjournals.org)
CD4+ T-cell depletion abrogated infiltration of NK, dendritic, and CD8+ T cells in the tumors, implicating these populations as downstream effectors of fucosylation- and CD4+ T cell-triggered tumor suppression. (aacrjournals.org)
Knockdown of HLA- DRB1 and HLA-A in vivo revealed HLA-DRB1 is required for L-fucose-mediated tumor suppression, and notably, for recruitment of CD4+ T cells. (aacrjournals.org)
Our data show how increased fucosylation drives tumor suppression through CD4+ T cells, and support the potential of dietary L-fucose to boost immunity in melanomas. (aacrjournals.org)
2 Modulation of TME is also a strategy used for tumor suppression. (bdbiosciences.com)
The function of this gene has not yet been determined but may involve a role in tumor suppression. (nih.gov)

Therefore, dampening the ongoing inflammation, for instance by inhibiting pro-inflammatory cytokines, can indirectly lead to better Treg-mediated suppression. (medscape.com)
Indirect improvement of Treg function can also be achieved by enhancing responsiveness of effector cells to suppression. (medscape.com)
In Type 1 diabetes, inflammatory bowel disease and lupus, effector cells are refractory to inhibition by Treg. (medscape.com)
[ 20 , 26 ] Elucidating the cause of this resistance to suppression and subsequent targeting will enhance Treg-mediated inhibition and restrict uncontrolled activation of effector cells. (medscape.com)
In experimental autoimmune encephalomyelitis (EAE), it was found that Treg isolated from the CNS could suppress effector cells from the spleen, but failed to inhibit effector cells isolated from the site of inflammation. (medscape.com)
[ 130 ] Another study describing the negative effects of IL-6 on Treg-mediated suppression also found that IL-6 acts on effector cells rather than on Treg. (medscape.com)
[ 33 ] Similarly IL-7, known to reduce Treg-mediated suppression, is expected to target effector cells as well, [ 34 ] since expression of the IL-7 receptor (CD127) is low on Treg. (medscape.com)
[ 131 ] Therefore, blocking these pro-inflammatory cytokines will reduce the resistance of effector cells to suppression and thereby enhance control of inflammation by Treg. (medscape.com)
Therefore, in addition to enhancing T-cell activation, NX-1607 renders T cells resistant to Treg and TGF-β-mediated suppression. (bmj.com)
Here, we explored the characteristics and mechanistic basis of the Treg-intrinsic CTLA4/PKCη signaling pathway that we recently found to be required for contact-dependent Treg-mediated suppression. (jci.org)
We show that PKCη is required for the Treg-mediated suppression of tumor immunity in vivo. (jci.org)
It has been reported that the cytotoxic T lymphocyte antigen-4 (CTLA-4) receptor is constitutively expressed by regulatory T cells and a role for this molecule in Treg suppression has been suggested. (bham.ac.uk)
Here, we restricted immune responses to nonlymphoid tissues and used intravital microscopy to visualize Treg suppression of rejection by effector T cells (Teffs) within inflamed allogeneic islet transplants. (jci.org)

Phd1, Phd2, and Phd3 function redundantly as oxygen sensors in T lymphocytes to enable environmental oxygen to limit effector differentiation in vitro and in vivo. (nih.gov)
These data provide new insight into the success of checkpoint blockade for cancer immunotherapy, revealing T-bet as a key transcriptional regulator of tumor-reactive CD8 + T-cell effector differentiation under otherwise tolerizing conditions. (aacrjournals.org)
To identify Plcγ1 effector molecules involved in regulation of erythroid differentiation, we assessed changes occurring at the global transcriptional and DNA methylation level after inactivation of Plcγ1. (nih.gov)

The cell intrinsic mechanisms by which T lymphocyte behavior is modulated to promote local immune suppression within the lungs are incompletely elucidated. (nih.gov)
A promising approach to engage effector cells of the immune system overcoming some of the escape mechanisms has been introduced more than two decades ago. (mdpi.com)
Therefore, we aimed to determine the effector mechanisms by which subsets of tumor-infiltrating MDSC block T cell function. (nih.gov)
Interestingly, both MDSC subgroups inhibited T cells through nitric oxide (NO)-related pathways, but expressed different effector inhibitory mechanisms. (nih.gov)
These results suggest that MDSC subpopulations utilize independent effector mechanisms to regulate T cell function. (nih.gov)
The study provides new insight into mechanisms of TCDD-induced suppression of B cell effector function. (nih.gov)
Regulatory T cells function by a cell-cell contact dependent suppression of other T lymphocyte's proliferation and effector mechanisms. (nih.gov)
These results define novel mechanisms governing transcriptional activation of CTLA-4 in human effector CD4 T cells. (wayne.edu)
Many effector molecules have been proposed to have a central role in regulatory T cell function, and it is now clear that Tregs are equipped with multiple mechanisms by which to exert suppressive function. (bham.ac.uk)
By acting on key biological mechanisms responsible for tumor growth and immune suppression, STRs represent a promising small molecule approach for treating cancer. (altitudelsv.com)

The GTPases (GTP bound) interact with several effectors and modulate a number of different biological pathways including those that regulate cytoskeleton, cellular motility, cytokinesis, proliferation, apoptosis, transcription and nuclear signaling. (elsevierpure.com)
We found that G-MDSC had a higher ability to impair proliferation and expression of effector molecules in activated T cells, as compared to Mo-MDSC. (nih.gov)
While inhibition of PKC-q in effector T cells blocks proliferation and cytokine production, inhibition of PKC-q in regulatory T cells increases their suppressive activity. (nih.gov)
Proliferation of CD4+ effector T cells activated by anti-CD3/CD28 was suppressed when cultured 1:1 with Tregs or TGF-b. (bmj.com)
Unlike CD28, CTLA-4 interaction transmits a negative signal in T cells, leading to suppression of proliferation. (wayne.edu)
Upon antigen stimulation they rapidly upregulate glycolysis and oxygen to produce high levels of ATP and nucleotides required for cell proliferation and effector functions. (nih.gov)

Alterations in the Ras pathway and its downstream effectors are among the major drivers for uncontrolled cell growth in many cancers. (elsevierpure.com)
The top common downstream effector was H2afy2, which encodes for the histone variant macroH2A2 (mH2A2). (nih.gov)
SAN DIEGO, Jan. 09, 2020 (GLOBE NEWSWIRE) - eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulators (STRs) for the treatment of cancer, and Pfizer Inc. (NYSE: PFE) today announced an exclusive worldwide license and collaboration agreement to develop small-molecule inhibitors of eukaryotic initiation factor 4E (eIF4E), a key oncogenic driver located downstream from both the RAS and PI3K signaling pathways. (altitudelsv.com)

Ipilimumab treatment increased absolute lymphocyte counts, eosinophils, effector T cells and their activation status, whilst diminishing the suppressive side of the immune response, acting on regulatory T cells and myeloid derived suppressor cells (MDSCs). (oncotarget.com)

For a selected subset of CEAPs and candidate effectors, semiquantitative RT-PCR showed that these transcripts were either expressed constitutively in both in vitro and in planta or induced during plant infection. (biomedcentral.com)
2018) Suppression of the in vitro growth and development of Microdochium nivale by phosphite. (harper-adams.ac.uk)

Furthermore, adding both these cytokines to naïve effector cells reversed their responsiveness to suppression. (medscape.com)
3 The fourth generation of (CAR) design attempts to deliver cytokines to modulate the TME either by activating host effector T cells or hampering host suppressors and reinforcing memory T cells. (bdbiosciences.com)
These cytokine-producing CARs, called T cells redirected for universal cytokine killing (TRUCKs), can deliver a variety of cytokines, such as IL-12, IL-15, IL-18 or IL-21 to control immune effector functions. (bdbiosciences.com)
The presence of PKCη-deficient ( Prkch -/- ) Tregs in the tumor microenvironment was associated with a significantly increased expression of the costimulatory molecule CD86 on intratumoral CD103 + DCs, enhanced priming of antigen-specific CD8 + T cells, and greater levels of effector cytokines produced by these cells. (jci.org)

These may be novel therapeutic vaccines, effector cells displaying chimeric antigen receptors (CARs), antiviral antibodies, and other molecules. (nih.gov)

Tumours progress despite being infiltrated by tumour-specific effector T cells. (nih.gov)
Inhibitory immune cells such as regulatory T-cells (Tregs) may infiltrate the tumour and suppress the ability of other effector immune cells to kill cancer cells. (alive.com)

In turn T and B cells develop effector functions (cytokine production, cytotoxic function or specific antibody production) associated with a protective immune response that eliminates the offending (or invasive) agent. (nih.gov)

SR1001 binds specifically to the ligand-binding domains of RORα and RORγt, inducing a conformational change within the ligand-binding domain that encompasses the repositioning of helix 12 and leads to diminished affinity for co-activators and increased affinity for co-repressors, resulting in suppression of the receptors' transcriptional activity. (nature.com)
SLAM family receptors control pro-survival effectors in germinal center B cells to promote humoral immunity. (nih.gov)

Inhibition of these pathways is expected to specifically block MDSC subsets and overcome immune suppression in cancer. (nih.gov)

The applicant found that activation of H-Ras GTPase leads to suppression of integrin activation through the activation of ERK1/2 at the plasma membrane. (grantome.com)

In addition to the role in generating within root tissue the feeding cells essential for nematode development, nematode secreted effectors are becoming recognized as suppressors of plant immunity. (usda.gov)
APC) capture, process and present antigen to effector T and B cells (adaptive immunity). (nih.gov)

These primed, precursor cells (Thpp) produce IL-2 and proliferate rapidly, allowing expansion of antigen-specific cells during an immune response before commitment to a particular effector phenotype. (rochester.edu)
It remains unclear whether this suppression mechanism is mediated by direct T cell-T cell interactions or requires antigen presenting cells (APCs) as well. (biomedcentral.com)
The data obtained suggest that the CTLA-4 receptor may function on regulatory T cells by modulating CD80/CD86 co-stimulatory molecule expression by antigen-presenting cells, and hence their capacity to activate conventional T cells to generate effector T cells and instigate an effective immune response. (bham.ac.uk)

Using a murine model to study how effector CD8 + T-cell responses to tumors may be enhanced in a tolerizing environment, we identified a critical role for the T-box transcription factor T-bet. (aacrjournals.org)
20. Intact B7-H3 signaling promotes allograft prolongation through preferential suppression of Th1 effector responses. (nih.gov)
These results demonstrate that differential clinical responses to OIT are associated with both preexisting characteristics of peanut-reactive CD4+ T cells and suppression of a subset of Th2 cells. (jci.org)

The Th1 and Th2 subsets of CD4+ T cells induce different types of effector functions that are useful in combating different pathogens. (rochester.edu)

Over the course of OIT, we observed suppression of Th2 and Th1 gene signatures in effector clonotypes but not T follicular helper-like (Tfh-like) clonotypes. (jci.org)
2018) Supercoiling of an excised genomic island represses effector gene expression to prevent activation of host resistance. (harper-adams.ac.uk)

The coordinated expression of CD39/CD73 on Tregs and the adenosine A2A receptor on activated T effector cells generates immunosuppressive loops. (biolegend.com)
CTLA-4 is constitutively expressed on regulatory T cells (Tregs) but is also inducible in effector T cells. (wayne.edu)

Taken together, these results suggested that celastrol attenuated the IL‑1β‑induced pro‑inflammatory pathway in orbital fibroblasts from patients with GO, which was associated with the suppression of NF-κB activation. (spandidos-publications.com)
cytoplasmic domain through a Rap1 effector and that ERK1/2 blocks activation by regulating one or more of the elements in this pathway. (grantome.com)

The effector functions of regulatory T cells still remain unclear. (biomedcentral.com)

While of significant interest to those working on the immune biology of urothelial cancer and drug discovery, this work does not provide any mechanistic insights into the role of DUX4 and immune suppression and the assessment on clinical samples forms the discovery part of a biomarker program, requiring further cohorts for validation. (elifesciences.org)

Interestingly we found that transient expression of GrCEP12 in N. benthamiana leaves suppressed ROS production, the induction of a couple of PTI marker genes, and callose deposition triggered by the bacterial PAMP flg22, providing direct evidence that GrCEP12 indeed has an activity in PTI suppression. (usda.gov)

Thus, the increased resistance of effector cells at the site of inflammation in EAE mice is caused by TNF-α and IL-6 produced by these cells. (medscape.com)
CD39 is the dominant member of this family in the immune system and involved in suppression of inflammation and control of platelet activation. (biolegend.com)
CD39 is involved in suppression of inflammation and control of platelet activation. (biolegend.com)

Mistletoe therapy has been shown to reduce immune suppression associated with chemotherapy, improve quality of life, and extend survival in patients with breast and gynecological cancers. (alive.com)
Akt1 suppression in advanced cancers has been indicated to promote metastasis. (stanford.edu)
We look forward to working with eFFECTOR with the goal of bringing a promising new therapy to patients with various treatment-refractory cancers," said Jeff Settleman, Ph.D., senior vice president and chief scientific officer, oncology, worldwide research, development & medical, Pfizer. (altitudelsv.com)

Suppression depends on cellular interactions with APCs. (biomedcentral.com)

There is also a specific interest in therapeutic immune-based antiviral products being part of a cure armamentarium to be tested as part of HIV sustained suppression/eradication human clinical trials to determine safety and efficacy. (nih.gov)
eFFECTOR Therapeutics is a clinical-stage biopharmaceutical company at the forefront of an emerging class of therapeutics known as selective translation regulators or STRs. (altitudelsv.com)
eFFECTOR has entered into clinical collaboration agreements with a strategic alliance between Pfizer and Merck KGaA to study tomivosertib in combination with avelumab and separately with Merck & Co to evaluate tomivosertib in combination with KEYTRUDA. (altitudelsv.com)

This study provides new evidence for a role of nematode secreted effectors in host defense suppression and adds new knowledge of the molecular basis of G. rostochiensis parasitism. (usda.gov)

Those sustained suppression/eradication or cure trials may consist of the evaluation of multiple therapeutic components, including anti-checkpoint receptor antibodies, latency reversing agents, and anti-HIV receptor antibodies, in addition to defined anti-HIV immune based products. (nih.gov)

Under terms of the agreement, eFFECTOR will receive a $15 million payment upfront, and will be eligible for additional potential $492M in R&D funding, development and sales milestone payments. (altitudelsv.com)

Our results clearly demonstrated an activity of GrCEP12 in PTI suppression. (usda.gov)

Interestingly transgenic potato plants overexpressing the derived GrCEP12 peptide were more susceptible to nematode infection, indicating a role of GrCEP12 in host defense suppression. (usda.gov)

Addition of NX-1607 recovered the proliferative capacity of CD4+ effector T cells to levels equivalent to that of anti-CD3/CD28 stimulation alone. (bmj.com)

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