Researchers at the Yerkes National Primate Research Center, Emory University, have discovered a possible new mechanism by which sooty mangabeys, a natural host of simian immunodeficiency virus (SIV), avoid developing AIDS despite having very high viral loads. The study, available in the current issue of Blood, shows sooty mangabeys are able to maintain levels of CD4+ T cells by regenerating more rapidly their pool of naïve CD4+ T cells.
CD4+ T cells are a type of white blood cell key to maintaining the immune system and are important because they allow the immune system to respond to newly encountered microbes. This finding may help explain why SIV and HIV lead to AIDS in other nonhuman primates and humans, respectively, but not in the sooty mangabey.
In rhesus macaques infected with SIV, the virus kills CD4 + T cells, thus weakening the immune system. As these CD4+ T cells die, the body makes an attempt to replace them, but because the production of naïve cells is slower, this CD4+ T cell repopulation is ultimately ineffective and the infection progresses to AIDS. In contrast, SIV-infected sooty mangabeys may be better able to preserve a healthy level of CD4+ T cells due to a more effective T cell regeneration.
To investigate how production of T cells is regulated in nonhuman primates that experience a pathogenic or a non-pathogenic infection with SIV, researchers led by Mirko Paiardini, PhD, who recently joined the Division of Microbiology and Immunology at Yerkes, and collaborators from the National Institutes of Health, Seattle Biomed and the University of Utrecht (Holland) depleted the CD4+ T cells in healthy rhesus macaques as well as sooty mangabeys and studied the kind of T cells regenerated in each species.
“The results showed that while both species showed a similar extent of CD4+ T cell replenishment, the rhesus macaques regenerated their naïve CD4+ T cells more slowly,” says Paiardini. “In addition, we found repopulating CD4+ T cells in macaques may be more susceptible to virus infection. In the sooty mangabey, the replenished cells have a phenotype that likely makes them more resistant to SIV infection. These new findings have increased our understanding of the immune system and are critical to our continuing research to determine why some species are more susceptible than others to infectious diseases.
Building upon these findings, researchers are currently working to define the molecular profile and susceptibility to SIV infection of repopulating CD4+ T cells in sooty mangabeys and rhesus macaques.
For eight decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve the health and well-being of humans and nonhuman primates. Today, the center, as one of only eight National Institutes of Health-funded national primate research centers, provides leadership, training and resources to foster scientific creativity, collaboration and discoveries. Yerkes-based research is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate quality animal care.
Within the fields of microbiology and immunology, neurologic diseases, neuropharmacology, behavioral, cognitive and developmental neuroscience, and psychiatric disorders, the center’s research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases; treat drug addiction; interpret brain activity through imaging; increase understanding of progressive illnesses such as Alzheimer’s and Parkinson’s diseases; unlock the secrets of memory; determine how the interaction between genetics and society shape who we are; and advance knowledge about the evolutionary links between biology and behavior.
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.