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The Cutting Edge

Harnessing the Immune System to Control Disease

  Harnessing the Immune System to Control Disease
 

In atomic-force microscopy image of a T-cell, dark purple indicates stiffer sections and lighter purple represents softer spots. Image: Courtesy of Dr. Manish Butte

When the T-cell recognizes an antigen, it gives the cell presenting the antigen a “hug,” so to speak, instead of a handshake. This initial interaction causes the T-cell to search nearby to find other cells that are presenting the same antigen to give them “hugs” as well. UCLA researchers have discovered that after the initial hug, T-cells become more gregarious, giving something more like a bear hug to any cell presenting its antigen.

These larger hugs help to activate the T-cell, equipping it to go out into the body and coordinate multi-cellular attacks to fight infections or cancers. The UCLA team learned that how stiff or soft T-cells are controls their response — the cells react slowly when they are stiff and trigger easily when they are soft. “T-cells are like the shy person at the office holiday party who acts stiff until they loosen up a bit and then are all over the dance floor,” says Manish Butte, MD, PhD, associate professor of pediatrics and microbiology, immunology and molecular genetics.

Dr. Butte and his colleagues pioneered an approach using an instrument called an atomic-force microscope to make real-time observations about what excites T-cells at the nanoscale. Once they learned that T-cells soften after activation, the UCLA team identified the biochemical pathway that controls the cell’s stiffness. Then they identified drugs that can help the T-cells either elicit or subdue a response. The finding provides scientists with a new capability to manipulate the immune system, Dr. Butte says.

Diseases arise in people and animals when T-cells attack the body’s other cells, or when they fail to signal attacks against cancer cells or infectious pathogens. “Until now, we had a limited understanding of what controls T-cell activation,” says Dr. Butte, chief of pediatric allergy and immunology at UCLA Mattel Children’s Hospital and a member of the UCLA Children’s Discovery and Innovation Institute. “Now that we understand the precise steps taking place, our findings suggest that altering T-cell stiffness with drugs could one day help us thwart diseases where T-cells are too active or not active enough.”

Dr. Butte and his colleagues are beginning to apply these findings to diminish the role T-cells play in triggering type 1 diabetes. “We can’t talk about precision medicine and still use a sledgehammer to treat disease,” Dr. Butte says. “By exploiting the mechanism we discovered to soften T-cells, we could accelerate vaccine responses so a patient won’t need multiple boosters and months of waiting to get full immunity. Or we could stiffen up T-cells to prevent the body from rejecting transplanted organs.”

“Cytoskeletal Adaptivity Regulates T-cell Receptor Signaling,” Science Signaling, March 7, 2017


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IN THIS ISSUE
  • A New Era in Biomedical Education
  • Minimally Invasive Procedure Puts End to Boy’s Rare Form of Seizures
  • Implantable Medical Device Draws Energy Directly from Human Body
  • Study Illustrates Axon Growth in Developing Nervous System
  • Harnessing the Immune System to Control Disease
  • Gut-Brain Association in People with IBS
  • Conscious Sedation a Safe Alternative for Heart-valve Procedure
  • How Advanced Melanoma Resists Immunotherapy
  • Scientists Identify Brain Cells Involved in Pavlovian Response
  • Promising Finding for Children after Brain Injury
  • Combination Therapy Could Provide New Treatment for Ovarian Cancer
  • Vision Quest
  • Healing Body, Mind and Spirit
  • Home Improvement
  • The Nurture Rx
  • Promise Keeper
  • Awards/Honors
  • In Memoriam
  • Memory Lane
  • David Geffen, UCLA Leaders Dedicate Geffen Hall
  • Mattel, Inc. Commits $50 million to UCLA Mattel Children’s Hospital
  • UCLA Stein Eye Institute Celebrates 50th Anniversary and Reopening of Jules Stein Building
  • Kaleidoscope 5 Sheds Light on Pediatric Research
  • Tour De Pier Breaks Its Fundraising Record for Cancer Research
  • Longtime UCLA Supporter Honors Wife’s Memory
  • Friends Gather to Support Mental Health
  • Generations Join Together to Defeat Cancer
  • A Life Dedicated to Pediatric Ophthalmology
  • Semel Institute Introduces the 2016-2017 Max Gray Fellows
  • Stars Step Out for Cancer Research at Taste for a Cure
  • Lunch with the Scientists Highlights Women’s Research and Philanthropy
  • UCLA Women & Philanthropy Hosts Heart Health Seminar
  • Heart Heroes
  • Cam and Peter Starrett Establish a Term Chair in Urology
  • Community Conversations Open the Dialogue about Mental Health
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