The standard antiretroviral therapy suppress the human immunodeficiency virus (HIV) and stop the progression of HIV disease.
When someone is HIV-positive and takes antiretroviral drugs, the
virus persists in a reservoir of infected cells. Those cells hide out in
germinal centers, specialized areas of lymph nodes, which most "killer"
antiviral T cells don't have access to.
‘A group of antiviral T cells that have the entry code into germinal centers have been identified by researchers. This could help design better therapeutic vaccines, and efforts to suppress HIV long-term.’
Scientists at Yerkes National Primate Research Center, Emory
University, have identified a group of antiviral T cells that do have
the entry code into germinal centers, a molecule called CXCR5.
Knowing how to induce antiviral T cells displaying CXCR5 will be
important for designing better therapeutic vaccines, as well as efforts
to suppress HIV long-term, says Rama Rao Amara, professor of
microbiology and immunology at Yerkes National Primate Research Center
and Emory Vaccine Center.
The findings are published in PNAS
"We think these cells are good at putting pressure on the virus,"
Amara says. "They have access to the right locations - germinal centers -
and they're functionally superior."
Amara and his colleagues looked for these antiviral cells in
experiments with rhesus macaques, which were vaccinated against HIV's
relative SIV and then repeatedly exposed to SIV. The vaccine regimens were described in a previous publication.
The vaccines provided good but imperfect protection against
pathogenic SIV, which means that a group of 20 animals ended up
infected, with a range of viral levels. In some animals, a large
fraction (up to 40%) of anti-viral CD8 T cells in lymph nodes
displayed CXCR5. Having more CXCR5-positive antiviral T cells was
strongly associated with better viral control, the researchers found.
T cells can be divided into "helper" cells and "killer" cells, based
on their function and the molecules they have on their surfaces. A
group of T cells called follicular helper T cells or Tfh cells were
already known to be in germinal centers and to display CXCR5. Tfh cells
are also considered a major reservoir for HIV and SIV.
When stimulated outside the body, the CXCR5-positive cells can
attack and kill virus-infected Tfh cells. Some of the killer cells lose
CXCR5 upon stimulation, but adding an immune regulatory molecule called
TGF-beta can boost the CXCR5 levels.
Co-corresponding author Vijayakumar Velu, assistant professor
at Yerkes, says the CXCR5+ killer cells the team has identified have
stem cell-like properties, because they have the capacity to
differentiate into both CXCR5+ and CXCR5- cells. The lab of co-author
Rafi Ahmed, director of Emory Vaccine Center, has reported analogous
cells in mice with chronic viral infections. In addition, a recent Science Translational Medicine
paper found similar cells in HIV-infected humans, calling them "follicular CD8 T cells."
"These cells have the potential to infiltrate sites of ongoing viral
replication and persistence," Amara says. "Their properties and the
ability to induce these cells by vaccination provide a tremendous
opportunity to target and reduce the viral reservoir in lymphoid