Regulatory T Cells may Be what's Inhibiting the Development of a Successful Therapeutic HIV Vaccine

Regulatory T cells, which help to keep the immune system in check, may be one of the barriers to the development of a therapeutic HIV vaccine.

Regulatory T cells (Treg), which prevent the immune system from turning on itself by suppressing the immune response, may be limiting the ability to develop a therapeutic HIV vaccine, researchers at the University of Pittsburgh Medical Center have found.

The team of researchers, lead by Charles R. Rinaldo, Jr, PhD, professor and chairman, Department of Infectious Diseases and Microbiology, Pitt’s Graduate School of Public Health, designed the current study to evaluate the efficacy of a therapeutic dendritic cell-based HIV vaccine they developed to activate the CD8, or killer T cell, response in 2008. For the current study, the researchers removed Treg from the blood samples given during the earlier trial “and found it was masking a two-fold increase in immune response to HIV induced by the vaccine.”

“When we removed Treg from blood cells, we found a much stronger immune response to the vaccine, giving us insight into how we can develop more effective HIV vaccines,” said Rinaldo. “Treg normally shuts down CD8 responses once the infection has been controlled, but in this case it appears to be putting on the brakes early and possibly limiting the vaccine’s ability to do its job effectively.”

According to Rinaldo, one reason for this may be that HIV infection “drives up Treg, which in turn shuts down the HIV-1- specific CD8 T cell response.”

“We know how to treat HIV, but are still learning how to use immunotherapy strategies to completely flush it out of the body,” added Bernard J.C. Macatangay, MD, assistant director of the University of Pittsburgh Immunology Specialty Laboratory and lead author of the article in the current issue of PLoS ONE. “Our findings show Treg plays an important role, but we need to figure out how to maintain the right balance by getting around these cells without blocking them completely.”