Category: T-cells

Categories : COVID T-cellsTags :

Severe COVID May Lead to Stronger Immunity

On By ModernMedia

Researchers from La Jolla Institute for Immunology (LJI), The University of Liverpool and the University of Southampton have discovered that the degree of COVID severity appears to be linked to how long-lasting and strong the subsequent immunity is. 

“The data from this study suggest people with severe COVID-19 cases may have stronger long-term immunity,” said study co-leader LJI Professor Pandurangan Vijayanand, MD, PhD.

The research examines T-cells from COVID infections in unprecedently high detail.

“This study highlights the enormous variability in how human beings react to a viral challenge,” added co-leader Christian Ottensmeier, MD, PhD, FRCP, a professor at the University of Liverpool and adjunct professor at LJI.

Vijayanand and Ottensmeier have been studying how antibodies and the different subsets of T-cells control COVID disease severity. In this study, they examined CD8+ T-cells, which are the T-cells responsible for destroying virus-infected cells, and “memory” CD8+ T-cells are also important for guarding the body against reinfections of the same virus. These memory T-cells are poised to rapidly proliferate and engage their cell-destroying functions on subsequent antigen encounters. They can reside in peripheral organs and their memory can also be shaped by infection history.

Utilising a new technique called single-cell transcriptomics analysis, they were able to study expressions of individual genes of 80 000 CD8+ T-cells drawn from 39 COVID patients and from 10 non-exposed donors, whose blood samples had been taken before the pandemic. Of the COVID patients, 17 cases were mild and non-hospitalised, 13 were hospitalised and 9 had required ICU care.

Surprisingly, the researchers found that the strongest CD8+ T-cell responses were from those with the more severe form of the disease, and not the milder cases.”There is an inverse link between how poorly T cells work and how bad the infection is,” observed Ottensmeier. “I think that was quite unexpected.” A stronger response would be expected from CD8+ T-cells in mild cases due to having the resources of a better functioning immune system. However, the mild group of CD8+ T-cells showed signs of “exhaustion”, which happens when the immune system overloads the T-cells, causing them to lose effectiveness.

The researchers believe that it will be beneficial to study whether this phenomenon may hinder the ability to build long-term immunity.

“People who have severe disease are likely to end up with a good number of memory cells,” said Vijayanand. “People with milder disease have memory cells, but they seem exhausted and dysfunctional—so they might not be effective for long enough.

“What the researchers would like to look at next is to look at T-cells from lung tissue as opposed to blood samples, because that is where the infection hits hardest.

“This study is very much a first step in understanding the spectrum of immune responses against infectious agents,” said Ottensmeier. The researchers will also look at T-cells in cancer patients who are also infected with COVID.

Source: Medical Xpress

Journal information: Anthony Kusnadi et al, Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells, Science Immunology  21 Jan 2021: Vol. 6, Issue 55, eabe4782 DOI: 10.1126/sciimmunol.abe4782

Categories : Allergies T-cellsTags :

Itching in Severe Eczema Uses a Different Pathway

On By ModernMedia

A study shows that there are two molecular pathways for conveying sensations of itching, with the itching of severe eczema following an unexpected route.

In normal eczema, cells in the skin convey the itching sensation, releasing histamines. This can be blocked with antihistamines.

“Years ago, we used to think that itch and pain were carried along the same subway lines in the nerves to the brain, but it turned out they weren’t, and these new findings show there’s another pathway entirely that’s causing these episodes of acute itching in eczema patients,” said principal investigator Brian S Kim, MD, Washington University School of Medicine. “The itch can be maddening. Patients may rate their chronic itch at around a 5 on a scale of 10, but that goes up to 10 during acute itch flares. Now that we know those acute flares are being transmitted in an entirely different way, we can target that pathway, and maybe we can help those patients.”

With severe itching in eczema, different cells in the blood are activated, transmitting great quantities of non-histamine molecules which also convey the itching sensation. This renders antihistamines usesles in trying to control the itch. The discovery of this new pathway offers new possibilities for treating other conditions as well. Recent studies have tried to block Immunoglobulin E (IgE) in response to allergies.

“We’ve connected acute itching in eczema to allergic reactions transmitted by an entirely different population of cells,” explained Kim. “In patients who experience episodes of acute itching, their bodies react in the same way as in people with acute allergy. If we can block this pathway with drugs, it might represent a strategy for treating not only itch but other problems, including perhaps hay fever and asthma.”

The team found that when mice with eczema made IgE in response to environmental allergens, they began to itch. However, instead of activating mast cells which produced histamine, the IgE activated basophils (a kind of white blood cell), activating a different nerve pathway to normal itching.

The discovery that eczema is exacerbated by allergens may help people avoid severe itching episodes, as well has helping the development of new targets for treatment.

Source: News-Medical.Net

Journal information: Wang, F., et al, A basophil-neuronal axis promotes itch. Cell, 2021 doi.org/10.1016/j.cell.2020.12.033.

Categories : Diseases, Syndromes and Conditions T-cellsTags :

New Study Reveals T-Cell Role in Periodontitis and Bone Loss

On By ModernMedia

There are mechanisms involved in diseases of bone loss, such as periodontitis that are still not well understood, but an unexpected behaviour of a type of T-cell may shed new light on the matter.

Looking at periodontal disease in mice, scientists found that regulatory T (Treg) cells start behaving unexpectedly. They lose their ability to regulate bone loss and begin to promote inflammation instead.

“That is important because, in many therapies analyzed in in-vivo models, researchers usually check if the number of regulatory T cells has increased. But they should check if these cells are indeed functioning,” said lead author Dr Carla Alvarez, a postdoctoral researcher at the Forsyth Institute.

In periodontal disease, bone loss occurs because the immune system responds disproportionately, destroying tissue through inflammation. The Treg cells normally suppress the immune system but lose the ability to do so during periodontal disease.

Understanding this falls into the field of osteoimmunology, which is about understanding the interaction of bone metabolism and the immune system. “This is an interesting mechanism highlighting how the bone loss is taking place in periodontal disease,” said Dr Alpdogan Kantarci, at Forsyth and co-author of the paper.

A potential treatment for periodontal disease would involve reactivating the Treg cell’s immunosuppression function, but this is a complex, nonlinear task complicated by the fact that periodontal disease is initiated by oral microbes.

“The relationship between immune response and bone is not so straightforward,” said Alvarez. “There are multiple components. You have to imagine a complex network of signaling and cells that participate.”
The researchers’ next step is to examine the process in humans.

Source:Medical Xpress

Journal information: Alvarez, C., Suliman, S., Almarhoumi, R. et al. Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis. Sci Rep 10, 19018 (2020). doi.org/10.1038/s41598-020-76038-w

Categories : Diseases, Syndromes and Conditions T-cellsTags :

Ginger Promising in Countering Autoimmune Diseases

On By ModernMedia

A pre-clinical study has shown that the common herbal remedy and condiment, ginger, may be effective in countering some autoimmune disease mechanisms.

It is already known that ginger has some anti-inflammatory and anti-oxidative properties, making it a popular herbal remedy for inflammatory conditions.Out of at least 14 bioactive compounds, 6-gingerol, which also gives it its distinctive aroma and taste, is reported by a news study to be therapeutic in countering certain autoimmune disease mechanisms in mice.
In mice with antiphospholipid syndrome or lupus, 6-gingerol inhibited the release of neutrophil extracellular traps, which is triggered in response to the autoantibodies produced by these diseases. 

“Neutrophil extracellular traps, or NETs, come from white blood cells called neutrophils,” said lead author Ramadan Ali, PhD. “These sticky spider-web like structures are formed when autoantibodies interact with receptors on the neutrophil’s surface.”

According to Ali, these webs play an important role in the pathogenesis of lupus and antiphospholipid syndrome where they trigger autoantibody formation and contribute to blood vessel clotting and damage.

The premise of the study was: “Will the anti-inflammatory properties of ginger extend to neutrophils, and specifically, can this natural medicine stop neutrophils from making NETs that contribute to disease progression?”
“This pre-clinical study in mice offers a surprising and exciting, ‘yes’,” Ali said.

The researchers discovered that after giving 6-gingerol, the mice had lower levels of NETs. Clot formation tendency was drastically reduced and 6-gingerol seemed to inhibit neutrophil enzymes called phosphodiesterases, in turn lowering neutrophil activation.

All of the mice had reduced autoantibodies, suggesting a disruption of the inflammatory cycle of autoantibodies stimulating NETs which stimulate more autoantibodies.

Study author and rheumatologist Jason Knight, MD, noted that patients often asked about herbal supplements, about which he had not been taught much. However, the pre-clinical trial results show that 6-gingerol has anti-neutrophil properties that may be protective against autoimmune disease progression.

“As for basically all treatments in our field, one size does not fit all. But, I wonder if there is a subgroup of autoimmune patients with hyperactive neutrophils who might benefit from increased intake of 6-gingerol,” said Knight. “It will be important to study neutrophils before and after treatment so we can determine the subgroup most likely to see benefit.”
For a patient with active antiphospholipid syndrome or lupus, the bioactive compound cannot be the primary therapy, but the natural supplement may help those at high risk for disease development.

“Those that have autoantibodies, but don’t have activated disease, may benefit from this treatment if 6-gingerol proves to be a protective agent in humans as it does in mice,” Ali said.

“Patients with active disease take blood thinners, but what if there was also a natural supplement that helped reduce the amount of clots they produce? And what if we could decrease their autoantibodies?”

Source: Medical Xpress

Journal Information: Ramadan A. Ali et al, Anti-neutrophil properties of natural gingerols in models of lupus, JCI Insight (2020). DOI: 10.1172/jci.insight.138385

Categories : Genetics HIV T-cellsTags :

Long-term HIV Immunisation in Mice with Gene Technology

On By ModernMedia

While some COVID vaccines are entering the final phases of approval less than a year before the disease was first identified, HIV still has no vaccine after decades of research.

Now, engineered immune cells have elicited a response against HIV in mice, presenting an important first step forward in the quest for a vaccine. These broadly neutralising antibodies (bnabs) are effective against a variety of viruses and neutralise the glycan protecting HIV’s proteins.

Previous research had engineered B cells that produced the same antibodies as seen in rare HIV patients who are able to produce bnabs against HIV after many years. Now, this research has shown that it was possible to mature these into memory and plasma cells, conferring long-lasting protection and even showing improved antibodies can be produced, as in the immunisation process.

Principal investigator James Voss, PhD, of Scripps Research said, “This is the first time it has been shown that modified B cells can create a durable engineered antibody response in a relevant animal model.”

Currently it appears it would be an expensive therapy and a great barrier to many of the 38 million living with HIV around the world. A blood draw would be taken to the lab to engineer a vaccine for the patient, but Voss says that his team is looking to make the procedure inexpensive.

“People think of cell therapies as being very expensive,” Voss said. “We’re doing a lot of work towards trying to make the technology affordable as a preventative HIV vaccine or functional cure that would replace daily antiviral therapy.”

Source: Science Daily

Categories : HIV T-cellsTags :

T-cells can detect HIV-1

On By ModernMedia

A new study reported by News 24 shows that T-cells can detect HIV-1 in patients years after commencing antiretroviral therapy (ART): 

In the HIV-1 proteome (the entire set of proteins expressed by the virus) for each participant, the team identified T-cell epitopes (regions of proteins that trigger an immune response). They sequenced HIV-1 ‘outgrowth’ viruses from resting CD4+ T cells and tested mutations in T-cell epitopes for their effect on the size of the T-cell response.

These strategies revealed that the majority (68%) of T-cell epitopes did not harbour any detectable escape mutations, meaning they could be recognised by circulating T cells.

“Our findings show that the majority of HIV-1-specific T cells in people on ART can detect HIV viruses that have the capacity to rebound following treatment interruption,” concludes senior author Nilu Goonetilleke, a faculty member at the Department of Microbiology and Immunology, University of North Carolina at Chapel Hill.