Chronic infections are able to suppress the immune T-cell response over time, whereby it poses one of the biggest challenges to treating infectious diseases and developing preventive vaccines.
Upon studying a mouse model, the researchers found that a chronic strain of lymphocytic choriomeningitis virus (LCMV) targeted a type of stromal cells in the lymphoid organs called fibroblastic reticular cells (FRC)—which provide a three-dimensional framework used by immune cells to travel and interact with other immune cells within the lymphoid organs, such as spleen and lymph nodes.
The researchers say that widespread infection of the FRC caused a disruption of the function of the important stromal cells.
The study conducted by Dr. Scott N. Mueller, a postdoctoral fellow in the laboratory of Emory Vaccine Center Director Dr. Rafi Ahmed, showed that infection of FRC might involve a pathway called PD-1, which was found to block the immune response to the chronic strain of LCMV in a previous study.
According to the researchers, the major ligand (binding molecule) for PD-1, PD-L1, is upregulated on FRC after infection. They say that the PD-1 pathway may inhibit interactions between CD8+ T cells and FRC, preventing destruction of the FRC architecture in the spleen.
The researchers believe that all this may help the virus to remain in infected FRC, and contribute to long-term viral persistence.
"This research helps explain how the T-cell response can be suppressed in chronic viral infections," says Dr. Mueller.
"As we learn more about the intricate mechanisms involved we will be able to develop better treatments, and potentially preventive vaccines, for chronic infections such as those caused by HIV and hepatitis C viruses," he added.
The study has been reported online in the Proceedings of the National Academy of Sciences.