Emory Researchers Uncover Specialized Immune Cells that Can Reach HIV’s Hiding Spots

May 11, 2022

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Lisa Newbern, 404-727-7709, lisa.newbern@emory.edu

Emory Researchers Uncover Specialized Immune Cells that Can Reach HIV’s Hiding Spots

Researchers who study HIV are intent on discovering more details about how the immune system responds to infection so they can develop better treatments. In a recent study, researchers at the Emory National Primate Research Center (EPC) identified a novel subset of immune cells that appear to reduce the levels of virus in the blood and believe earning how to harness these cells could lead to new HIV treatments. The paper, which used a model of SIV infection in rhesus macaques, was published in JCI Insight.

One reason HIV is hard to fully eliminate is because of its ability to escape drug treatment by hiding in the body. Previous research has shown lymphoid tissues, including the lymph nodes and spleen, serve as a major reservoir for infected cells. In particular, infected cells hole up in an area of the lymph tissue called the B cell follicles. Immune cells, including T cells and natural killer (NK) cells, whose job is to kill virally infected cells, are generally unable to reach the B cell follicles. This makes the follicles a safe space for the virus.

Although it’s rare to find cytotoxic cells in these germinal centers, an earlier study from EPC researchers, published in the Proceedings of the National Academy of Sciences in 2017, found cytotoxic CD8+ T cells are able to traffic to B cell follicles during SIV infection.

The researchers decided to look at whether NK cells, another type of cytotoxic cells, also play a role in viral control. To do so, the research team studied rhesus macaques with chronic SIV infection. These animals are an important translational model system for studying HIV infection in humans. Within the B cell follicles of the animals’ lymph tissue, they found a subset of NK cells called CXCR5+ NK cells. Unlike most NK cells, these cells localize specifically to the B cell follicles. Additionally, the CXCR5+ NK cells appear to be effective at killing cells infected with SIV.

“Infiltration of these highly cytotoxic NK cells in the B cell follicles has never been shown before during chronic HIV/SIV,” says senior author Vijayakumar Velu, PhD, an assistant professor in the Division of Microbiology and Immunology at the EPC. “This study has implications for developing new cure strategies for HIV, as these cells traffic to B cell follicles during controlled infection,” says co-author Rama Amara, PhD.

Further study of the CXCR5+ NK cells revealed they express a receptor that enables them to home in on the B cell follicles. The researchers used a number of lab techniques, including multicolor flow cytometry and immunohistochemistry techniques, to confirm this infiltration occurs. RNA analysis also revealed the differences in gene expression in CXCR5+ NK cells compared with other types of NK cells. In the animal models, the presence of this subset of NK cells in the lymph tissue was associated with reduced levels of SIV RNA in the blood plasma.

The investigators further showed treatment with the cytokines IL-12 and IL-15 enhanced the generation and proliferation of these highly functional CXCR5+ NK cells. “This research suggests a way to boost the production and activity of these specialized cells,” says first author Sheikh Abdul Rahman, PhD, a research associate in the Division of Microbiology and Immunology.

The researchers acknowledge more research is needed before this promising approach can be studied in the clinic. In their next studies, they will look at the role of NK cells in the early phase of SIV infection, seek to determine if CXCR5+ NK cells kill infected cells in the lymph nodes and investigate the role of CXCR5+ NK cells during HIV/SIV vaccination.

Other contributors include coauthors James Billinglsley, PhD, Ashish Arunkumar Sharma, PhD, Tiffany M. Styles, PhD, Sakthivel Govindaraj, PhD, Uma Shanmugasundaram, PhD, Hemalatha Babu, PhD, Susan Pereira Riberio, PhD, Gregory Tharp, Chris Ibegbu PhD, Rafick P Sekaly, PhD, Steve Bosinger, PhD, Paul Johnson, MD. all from Emory University, as well as  Francois Villinger DVM, PhD, director of the New Iberia Research Center, University of Louisiana at Lafayette, and Stephen Waggoner, PhD, at University of Cincinnati College of Medicine.

Funding:

The research reported in this release is supported in part by the by the Emory National Primate Research Center base grants from the NIH Office of the Director as well as several NIH institutes. The publication contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by, NIH/HHS or the U.S. Government.

Grant numbers are listed below. Full grant amounts (direct + indirect) will be added.

NIH/OD:

P51OD011132, $10,751,414/year for 5 years

R24 OD010947

S10 OD026799

U42 OD011023

NIH/NIAID:

P30AI050409

R01AI148080

R01 AI148377

U19 AI109633

NIH/NICHD:

R01HD095741

Note: Only a portion of each grant supported the research reported in this news release.

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 $88 million in research funding (all sources, fiscal year 2021). 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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