CD8+ T Cells Increasingly Crucial in Pursuit of a Cure for HIV
June 25, 2024
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Lisa Newbern
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Emory researchers have identified a subset of lymph node CD8+ T cells, TCF1+CD39+CD8+, that drive a strong immune response to inhibit simian immunodeficiency virus (SIV) despite limiting the expression of the typical ("canonical") molecules CD8 T cells use to kill infected targets. Such a deeper understanding of how T cells limit SIV persistence and promote SIV control is critical to developing therapeutic strategies for curing human immunodeficiency virus (HIV) and improving life for the 39 million people who live with the disease.
The study results are reported in Nature Immunology.
"Harnessing CD8+ T cell functions is imperative toward an HIV cure," says Mirko Paiardini, PhD, Microbiology and Immunology division chief at the Emory National Primate Research Center. "This population of CD8+ T cells contributes to limiting SIV and HIV persistence by better controlling the virus and lowering viral reservoirs where the virus is known to hide." Paiardini is also a professor of Pathology and Laboratory Medicine at the Emory School of Medicine, contact principal investigator for ERASE HIV and co-director of the Next Generation Therapeutics Scientific Working Group at the Emory Center for AIDS Research.
"Based on our latest study results, these previously undescribed T cells may be first in line to fuel the SIV/HIV-specific response and assist in clearing the virus from the human body," said Zachary Strongin, first author of the paper who is senior scientist, Discovery Immunology at Merck and a former graduate student in the Paiardini lab.
To design better T cell therapy approaches for HIV cure, Paiardini and his colleagues aimed to understand the reactions and relevance of specific CD8+ T cell subsets, with a particular focus on lymph node cells, following HIV infection. Lymph nodes are a primary site of viral replication and previous demonstrations of unique CD8+ T cell biology.
The researchers worked with rhesus macaques, a highly characterized animal model for SIV infection, and analyzed lymph node biopsies at varying timepoints post-infection, an approach that facilitated the research team's identification of the TCF1+CD39+CD8+ T cell population. The researchers determined these T cells are unique in expressing markers of terminally differentiated cells, which are better equipped to kill infected cells, while also lacking well-known killing molecules, maintaining features of stemness and remaining functional without getting exhausted.
The Emory researchers' findings also highlight the value of exploring cell populations across diverse diseases. The populations the Emory researchers describe and their reactions after infection seem distinct from those reported in lymphocytic choriomeningitis virus (LCMV) and cancer studies, which provided the Emory team with indispensable insight into how CD8+ T cells function.
"Our observations highlight an opportunity to further explore the dynamics of CD8+ T cells at additional stages of infection as well as at additional tissue sites," says Laurence Raymond Marchand, MS.c, co-first author, who is a visiting scientist in the Paiardini lab. "It will also be important for our team to understand how well these cells respond to HIV cure interventions, which could inform future study designs, and how effective such interventions are beyond lymphoid tissues in the pursuit of an HIV cure."
Many on this Emory research team are part of the ERASE HIV Martin Delaney Collaboratory for HIV Cure Research. This NIH-funded research collaboratory seeks to characterize the key immune system functions that control persistent HIV infection and design innovative, immune-based therapies to eliminate or control the virus in the absence of antiretroviral therapy (ART). The ERASE HIV team also works with SisterLove, Inc., the first women's HIV/AIDS and reproductive justice organization in the Southeastern United States, to share ERASE HIV research advancements with all those SisterLove educates, inspires and serves.
Additional research collaborators on this study are Haydn Kissick, PhD, an assistant professor in Emory's Department of Urology with a joint appointment in the Department of Microbiology and Immunology at Emory University School of Medicine Mike Betts, PhD, professor of Microbiology in the Department of Microbiology at the Perelman School of Medicine at the University of Pennsylvania; and Claire Deleage, PhD, head, Tissue Analysis and Retroviral Protein Chemistry Core, at the Frederick National Laboratory for Cancer Research at the National Cancer Institute (NCI).
Funding
The research reported in this release is supported in part by the by the Emory National Primate Research Center's base grant from the NIH Office of the Director, other NIH institutes (NIAID, NCI, NHLB, NIDDK, NINDS and NIDA) and international funding (Mexican government and Vetenskapsrådet/Swedish Research Council). The publication contents are those of the author(s) and do not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. government. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Dedicated to discovering causes, preventions, treatments and cures, the Emory National Primate Research Center (EPC), 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 $90 million in research funding (all sources, fiscal year 2023). EPC 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.
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