Emory Researchers Find T Cell Responses Key for Controlling Asymptomatic TB
June 28, 2020
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Lisa Newbern
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In the first study to report on temporal dynamics of Mycobacterium tuberculosis (Mtb)-specific T cell responses in latent Mtb infection, researchers at Emory University showed the T cell response emerged as early as three weeks post infection and persisted throughout the six-month study. Such a rapid T cell response proved critical in controlling asymptomatic TB and is a key finding that will be important for designing better vaccines and treatments to control the disease. The study results appear in JCI insight.
"Because TB is the leading infectious disease killer, claiming 1.5 million lives every year, we want to know why some people who are infected with Mtb progress to TB disease while others remain asymptomatic and do not," says Jyothi Rengarajan, PhD, lead author and associate professor of medicine, Division of Infectious Diseases, Emory University School of Medicine and a researcher at the Emory Vaccine Center and Yerkes National Primate Research Center. "This important but poorly understood area of TB infection is difficult to assess in humans, so we were fortunate to work with nonhuman primates. Monkeys develop and respond to latent TB infection similar to the way humans do, which makes them an excellent translational model for studying the immunological basis for asymptomatic TB and then applying the results to humans and animals," she continues.
In the study, the researchers worked with an aerosol model of TB and compared responses of CD4 and CD8 T cells in blood, airways and lungs.
"We found significantly higher frequencies of T cell responses in the airways and lungs than we did in blood," says co-author Vijayakumar Velu, PhD, assistant professor at Yerkes. The specificity of where to activate T cells will help guide the development of better treatments and even a vaccine to prevent TB infections," he continues.
Uma Shanmugasundaram, PhD, assistant research scientist at Yerkes, is first author of the study. Other contributors include coauthors Melanie Quezada and Chris Ibegbu, PhD, both at Emory, as well as Deepak Kaushal, PhD, director of the Southwest National Primate Research Center, and colleagues at Texas Biomedical Research Institute and Tulane University.
This study on asymptomatic TB is also important for understanding how HIV drives reactivation of latent TB. In a related study from the Rengarajan and Kaushal research teams that was published in the Journal of Clinical Investigation, the researchers used a rhesus macaque Mtb/SIV co-infection model to study the role of SIV and anti-retroviral therapy (ART) in reactivation of latent TB. This study revealed ART fails to restore CD4 T cells in the lungs, which may help explain, in part, why some people co-infected with Mtb and HIV develop TB despite ART.
The study on asymptomatic TB was funded by the National Institutes of Health. Grant amounts (direct + indirect) are:
- R01AI111943, $890,058/yr
- R01AI123047, $899,688/yr
- R01AI134240, $908,608/yr
- P51OD011133, $7,939,355/yr
- P51OD011104, $8,470,444/yr
- P51OD011132, $10,540,602/yr
The study on Mtb/SIV co-infection was also funded by the National Institutes of Health. Grant amounts (direct + indirect) are:
- R01AI111943, $890,058/yr
- R01AI123047, $899,688/yr
- R01AI111914, $800,095/yr
- R01AI134240, $908,608/yr
- U19AI111211, $2,872,556/yr
- P51OD011133, $7,939,355/yr
- P51OD011104, $8,470,444/yr
- P51OD011132, $10,540,602/yr
Note: Amounts listed are for the full grants; only a portion of the grant funding was applied to the studies reported in this news release.
Dedicated to discovering causes, preventions, treatments and cures, the Yerkes National Primate Research Center (NPRC), part of Emory University's Robert W. Woodruff Health Sciences Center, is fighting diseases and improving human health and lives worldwide. The center, one of only seven NPRCs the National Institutes of Health (NIH) funds, is supported by more than $74 million in research funding (all sources, fiscal year 2019). Yerkes researchers are making landmark discoveries in microbiology and immunology; neurologic diseases; neuropharmacology; behavioral, cognitive, and developmental neuroscience; and psychiatric disorders. Since 1984, the center has been fully accredited by the AAALAC International, regarded as the gold seal of approval for laboratory animal care. For more information about Yerkes and the seven NPRCs, visit NPRC.org and follow us at @NPRCnews.
The Emory Vaccine Center mission is to improve human health by conducting fundamental and clinical research that leads to the development of effective vaccines against diseases of global importance.
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The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.