Our immune system has an incredible ability; it can remember infections it has already encountered, and when the body has another encounter with the invader, the response from the immune system is rapid and efficient. While some of the details of this process are understood, many questions remain. New work by investigators at the University of California, Berkeley, in collaboration with investigators at Emory University has shown that some of the same immune cells that battle the original infection hang around, reminding alive for years. Those cells develop unique characteristics that enable them to spring into action if the invader returns.
This work, reported in Nature, tracked a type of immune cell after exposure to a vaccine, so they could observe the development of long-term immunity. The immune cells that were watched, T cells, were followed after a yellow-fever vaccine, using a technology that monitors cells over long periods of time. The research indicated that one kind of T cell, CD8+ T cells, grew rapidly after the vaccine was administered, then they began to evolve about four weeks later. They became memory cells, which are able to live about ten times longer than T cells typically do.
"This work addressed fundamental questions about the origin and longevity of human memory CD8+ T cells generated after an acute infection," said senior co-author Marc Hellerstein, Professor of Nutritional Science and Toxicology at UC Berkeley. "Understanding the basis of effective long-term immune memory may help scientists develop better vaccines, understand differences among diseases and diagnose the quality of an individual person's immune responses."
Infections and vaccines stimulate the immune system, causing cells that have never been used, naive cells, to start reproducing, generating a pool of cells that can fight invaders, memory cells. That memory cell pool shrinks over time, and long-term memory cells are created. They are meant to provide protection over a much longer period. There has been debate about how these cells are maintained.
It seems that these cells take on several features to keep the long-term pool up over time. Using genes, they disguise themselves as memory cells, but they retain a genetic modification called methylation. Their methylation pattern indicates they are battle-scarred infection fighters called effector cells.
"These cells are like veteran soldiers, camped in the blood and tissues where they fight their battles, waiting for yellow fever to show up," said Hellerstein. "They are resting quietly and they wear the clothes of untested new recruits, but they are deeply experienced, ready to spring into action and primed to expand wildly and attack aggressively if invaders return."
It was not clear whether long-term memory cells underwent an effector phase, or if they had their own pathway. But a subset of cells in the effector pool was found to stay alive as long as long-term memory cells.
"These results make it clear that true long-term memory cells were once effector cells that have become quiescent," Hellerstein said. "This apparently keeps them poised to respond rapidly as new effector cells upon re-exposure to the pathogen."
It was determined that the half-life of long-term memory cells is 450 days, while T cells have a half-life of about 30 days, generally experiencing repeated exposure to common environmental antigens. As the memory pool becomes dormant, the unique cells have a fingerprint of original exposure and can respond rapidly if the pathogen is encountered again.
"The combination of molecular evidence of a unique life history with direct measurement of their long lifespan is what gives this study such power," Hellerstein said. "The technology to measure the dynamics of the birth and death of cells and advances allowing it to be applied to very small numbers of cells let this study happen."
Learn more about long-term immunity from the video above by Yale University.