Author Archives: ev1

Deep TCR sequencing reveals extensive renewal of the T cell repertoire following autologous stem cell transplant in MS

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A new study describes the complexity of the new T cell repertoire following immune-depleting therapy to treat multiple sclerosis, improving our understanding of immune tolerance and clinical outcomes.

In the Immune Tolerance Network's (ITN) HALT-MS study, 24 patients with relapsing, remitting multiple sclerosis received high-dose immunosuppression followed by a transplant of their own stem cells, called an autologous stem cell transplant, to potentially reprogram the immune system so that it stops attacking the brain and spinal cord. Data published in the Journal of Clinical Investigation quantified and characterized T cell populations following this aggressive regimen to understand how the reconstituting immune system is related to patient outcomes.

ITN investigators used a high-throughput, deep-sequencing technology (Adaptive Biotechnologies, ImmunoSEQTM Platform) to analyze the T cell receptor (TCR) sequences in CD4+ and CD8+ cells to compare the repertoire at baseline pre-transplant, two months post-transplant and 12 months post-transplant.

Using this approach, alongside conventional flow cytometry, the investigators found that CD4+ and CD8+ lymphocytes exhibit different reconstitution patterns following transplantation. The scientists observed that the dominant CD8+ T cell clones present at baseline were expanded at 12 months post-transplant, suggesting these clones were not effectively eradicated during treatment. In contrast, the dominant CD4+ T cell clones present at baseline were undetectable at 12 months, and the reconstituted CD4+ T cell repertoire was predominantly composed of new clones.

The results also suggest the possibility that differences in repertoire diversity early in the reconstitution process might be associated with clinical outcomes. Nineteen patients who responded to treatment had a more diverse repertoire two months following transplant compared to four patients who did not respond. Despite the low number of non-responders, these comparisons approached statistical significance and point to the possibility that complexity in the T cell compartment may be important for establishing immune tolerance.

This is one of the first studies to quantitatively compare the baseline T cell repertoire with the reconstituted repertoire following autologous stem cell transplant, and provides a previously unseen in-depth analysis of how the immune system reconstitutes itself following immune-depleting therapy.

About The Immune Tolerance Network

The Immune Tolerance Network (ITN) is a research consortium sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The ITN develops and conducts clinical and mechanistic studies of immune tolerance therapies designed to prevent disease-causing immune responses, without compromising the natural protective properties of the immune system. Visit http://www.immunetolerance.org for more information.

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The above story is based on materials provided by Immune Tolerance Network. Note: Materials may be edited for content and length.

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Deep TCR sequencing reveals extensive renewal of the T cell repertoire following autologous stem cell transplant in MS

Center for Electron Paramagnetic Resonance (EPR) Imaging in Vivo Physiology – University of Chicago – Video

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Center for Electron Paramagnetic Resonance (EPR) Imaging in Vivo Physiology - University of Chicago
The Center for Electron Paramagnetic Resonance (EPR) Imaging in Vivo Physiology is a consortium of institutions working to invent in Vivo imagers. The Center...

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Center for Electron Paramagnetic Resonance (EPR) Imaging in Vivo Physiology - University of Chicago - Video

Blazing trails in brain science

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Dr. Tom Insel, the longest-tenured director of the National Institute of Mental Health in almost half a century in Rockville | credits: New York Times Service

The police arrived at the house just after breakfast, dressed in full riot gear, and set up a perimeter at the front and back. Not long after, animal rights marchers began filling the street: scores of people, young and old, yelling accusations of murder and abuse, invoking Hitler, as neighbors stepped out onto their porches and stared.

It was 1997, in Decatur, Ga. The demonstrators had clashed with the police that week, at the Yerkes National Primate Research Centre at nearby Emory University, but this time, they were paying a personal call on the house of the centres director, inside with his wife and two teenage children.

I think it affected the three of them more than it did me, honestly, said Dr. Thomas R. Insel, shaking his head at the memory. But the university insisted on moving all of us to a safe place for a few days, to an undisclosed location.

Ill say this. I learned that if youre going to take a stand, youre going to make some people really angry so youd better believe in what youre doing, and believe it completely.

For the past 11 years, Insel, a 62-year-old brain scientist, has run an equally contentious but far more influential outfit: the National Institute of Mental Health, the worlds leading backer of behavioral health research.

Insel has not merely survived; he is the longest-serving director since Dr. Robert H. Felix, the agencys founder, retired almost a half-century ago. His tenure stretches over three presidencies and, more important, coincides with a top-down overhaul in the substance and direction of behavioral science.

The extent of this remodeling is not widely understood outside scientific circles nor universally appreciated within them. But in recent months, its author has begun to reveal his instincts publicly, in blog posts and speeches.

Last summer, he questioned whether people with schizophrenia should remain indefinitely on antipsychotic medications a shot at accepted medical wisdom.

A few months earlier, he had called out psychiatrys diagnostic encyclopedia, the DSM-5, as not scientifically valid, weeks before a new edition was released. Psychiatrists were not happy, and they told him so. Days later, he issued a statement saying that the manual was the best currently available, if imperfect.

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Blazing trails in brain science