In efforts to develop a vaccine against the AIDS-causing human immunodeficiency virus, most scientists focus on the direct-killing effect of CD8+ T-cells. But this is not optimal, suggest researchers at the UC Davis Health System and UC San Francisco.

In a study that appeared in the Jan. 28 edition of the open-access journal PLoS Pathogens, the UC researchers recommend finding and capitalizing on other virus-suppressing capabilities of CD8+ T-cells, also known as killer T-cells.

The same issue of the journal included the University of Pennsylvania's comparable study — one that arrived at similar results. In addition, the same issue of the journal included a commentary from a team at the University of New South Wales, Australia, describing the importance of the two studies.

“The cytotoxic activity of CD8+ T-cells by itself is not sufficient to provide ongoing protection from HIV because other virus-suppressive factors produced by these cells are involved,” said Satya Dandekar, senior study author, and professor and chair of the Department of Medical Microbiology and Immunology at UC Davis. “The dominant role of these cells in controlling viral infection has yet to be found and may not be entirely linked to their direct-killing abilities. These findings provide us a new direction in identifying the suppressive factors that can be used to prevent or halt HIV infection."

Lead researcher Joseph Wong, an associate professor of medicine at UCSF, said the outcome should inspire new efforts to identify the factors of CD8+ T-cells that can be leveraged against HIV.

“CD8+ T-cells are vital to an immune system response to viruses, but we clearly don’t know all the factors that make that possible,” said Wong, who was affiliated with the Veterans Administration San Diego Healthcare System and UC San Diego when the study was conducted.

Dandekar, Wong and their collaborators at UC Berkeley and UC San Diego conducted the research by studying rhesus macaque monkeys at the California National Primate Research Center at UC Davis — monkeys infected with simian immunodeficiency virus, or SIV.

SIV produces in monkeys the same disease that HIV produces in people. The researchers used antibodies to eliminate CD8+ T-cells from some of the monkeys and treated the animals with tenofovir and emtricitabine – the same highly active antiretroviral therapy, or HAART, medications used to treat HIV in people.

In animals with reduced CD8+ T-cells, the amount of virus increased dramatically, confirming that the cells have an important role in curtailing viral production. After treating the monkeys with HAART, however, virus levels declined at the same rate and degree, regardless of whether or not the monkeys had CD8+ T-cells.

Removal of CD8+ T cells did not alter the lifespan of virus-infected cells. If those cells were actively killing infected cells, the decline would have been much faster in monkeys with intact CD8+ T-cells.

Dandekar and Wong agreed that their outcome should encourage refinements of the existing HIV vaccine model. The study emphasizes the need to identify the noncytotoxic activities of CD8+ T-cells that can be replicated for immuno-therapeutics and vaccine design. New genomics technology can speed that process.

“We hope our finding stimulates a better understanding of what constitutes an effective immune response against HIV,” Wong said.

Other scientists involved in the research" Elizabeth Reay and Sumathi Sankaran-Walters of UC Davis; Satish Pillai of UCSF; Caroline Ignacio, David Looney, Theresa Russell and Matthew Strain of UC San Diego; and Rodin Porrata of UC Berkeley.

The National Institutes of Health supported the research.

Karen Finney is a senior public information officer for the UC Davis Health System.