A recent study conducted by scientists at UC Davis and UCSF may bring dramatic changes to the future of HIV vaccine research.
The study, published Jan. 28, revealed that the current research method of focusing solely on the ability of the body’s CD8 +T cells to kill infected cells neglects other virus-suppressing elements of these cells that may be vital to the production of a successful vaccine, said Satya Dandekar, senior study author and professor and chair of UC Davis’s Department of Medical Microbiology and Immunology [CQ].
CD 8 +T cells, white blood cells in the body activated to fight off a virus, have always been known to profoundly affect HIV. A set of studies completed at Harvard several years ago revealed that the removal of CD8 +T cells from infected animals caused an increase in HIV levels. Consequently, researchers assumed CD8 +T cells directly sought out and killed cells infected with the HIV virus, said Joseph Wong, lead researcher and associate professor of medicine at UCSF [CQ].
A small population of those infected with HIV is able to live for many years without treatment before contracting AIDS, Dandekar said. CD8 +T cells are credited with allowing individuals to depress the progress of the virus.
Dandekar and Wong, along with UC Davis Health System researchers, sought to find direct evidence for this function of CD8 +T cells in their study. They began by removing these cells from infected rhesus monkeys, and followed this by treating the animals with HIV drugs designed to prevent new cells from becoming infected with the virus.
“The hypothesis was that if infected cells are being eliminated by CD8 +T cells, infected cells should live longer after the removal of these CD8 +T cells, and virus levels should not come down as quickly” Wong said.
The results proved the opposite, however. The removal of CD8 +T cells had no effect on the virus levels in the bloodstreams of the infected animals.
These findings disprove the traditional school of thought regarding the function of CD8 +T cells in controlling HIV.
“CD8 +T cells must be doing something to control virus production, but it’s not through the classical mechanism that everyone assumed,” Wong said. “We need to understand what else is in the toolbox of CD8 +T cells that allow them to inhibit the virus.”
The results call into question the current strategies for developing a successful HIV vaccine. An opinion piece in the PLOS Pathogens journal cited the study as proving the role of CD8 +T cells in HIV as a “known unknown.”
“We all agree that CD8 +T cells are extremely important in limiting infection, but the question is: Do we know everything they do to achieve that viral control?” Dandekar said. “The answer from our study is no, we are not measuring everything that they do.”
If further studies confirm these findings, CD8 +T cells can be analyzed to determine their beneficial effects on decreasing the levels of infected cells in the body, Wong said.
“We can go back to examining how CD8 +T cells are working, and at some point if basic observations find a promising new mechanism, it would be nice to see that developed on animals and then in human studies,” he said.
MEGAN MURPHY can be reached at campus@theaggie.org.
