Active immune cells provide great protection against ischemic stroke

According to research published today in the Journal of Clinical Investigation by neurologists and immunologists at the University of Pittsburgh, a special subgroup of white blood cells provides mice with quick-acting and long-lasting protection against ischemic stroke.

The “first responders” to stroke were discovered in this study to be a novel fraction of CD8+ regulatory-like T cells or CD8+TRLs.

Within 24 hours of the commencement of a stroke, CD8+TRLs are drawn to the site of ischemia injury by a distinct “homing” signal emitted by dying brain cells. Once there, they release chemicals that have direct neuroprotective effects and reduce inflammation and subsequent brain damage.

The beauty of CD8+TRLs is in their fast response. They confer very potent protection to the brain, which can last a long time.”

Xiaoming Hu, MD, PhD, Study Co-Corresponding Author and Associate Professor, Neurology, University of Pittsburgh

Hu was also a U.S. Department of Veterans Affairs (VA) investigator. “Most importantly, these cells are easily accessible because they circulate in the blood before they enter the injured brain,” Hu added.

Creating shelf-stable and ready-to-use CD8+TRLs or developing a cocktail of neuroprotective signaling molecules released by those cells once they reach the brain could present effective future therapies against stroke and offer hope to hundreds of thousands of patients who are ineligible for treatments available to them currently.”

Jun Chen, MD, PhD, Study Co-Senior Author and Professor, Neurology, University of Pittsburgh

Chen was also a U.S. Department of VA investigator.

Every year, 800,000 Americans suffer from stroke, yet only 25% of those people will be qualified to receive one of the two FDA-approved treatments: tPA injections or mechanical thrombectomy, a surgical treatment in which the blood clot in the brain is removed with a stent retriever.

Many patients, especially those who live in rural places, are disqualified for those therapies since they must be given very soon after the stroke.

The 600,000 people who are still living are treated symptomatically and are at a high risk of protracted health issues, such as mobility issues and, in some instances, speech and cognitive disorders. Blood clot-busting therapy, in particular, has disadvantages that further restrict the number of patients who can benefit from it.

The immune system has a significant impact on stroke. The brain sends an “SOS” signal to the immune system the instant a blood clot lodges itself in a blood artery. This quick immune reaction seeks to eliminate cell remnants, reduce brain injury, and jump-start repair procedures.

However, the immune system’s functions are varied and complex and certain immune cell types may have specific advantageous or harmful effects on a damaged brain.

For the very first time, Chen, Hu, and their colleagues demonstrated that CD8+TRLs infiltrate the brain considerably more quickly than other regulatory immune cells. The size of the brain region hit by ischemia increased by 50% over the course of 24 hours after these unique CD8+TRLs were removed from the bloodstream of stroke mice. This is in contrast to animals whose CD8+TRL levels were preserved.

More encouragingly, mice who received a transfusion of lab-purified CD8+TRLs performed better and recovered more quickly than those who went untreated for more than five weeks.

Consequently, these distinct CD8+TRLs function as early responders to mobilize defenses following stroke and may team up with other immune cells to preserve the brain for a considerable amount of time.

Despite the efforts of thousands of people devoting their careers to finding treatments that could benefit stroke patients, therapy options are minimal. I have been working in this field for more than 30 years, and this is the first time I feel that I am seeing the light at the end of the tunnel, promising future clinical translation that will benefit patients.”

Jun Chen, MD, PhD, Study Co-Senior Author and Professor, Neurology, University of Pittsburgh