White Blood Cells "Remember” Prior Infections

A group of white blood cells, the gamma delta T cells, have been found to demonstrate "memory” characteristics that enable them to launch a sustained immune response against tuberculosis bacteria. This finding, reported in the March 22, 2002, issue of the journal Science, contributes important new insights as to how the immune system combats infection, a part of the continuing effort to develop a more effective tuberculosis vaccine.

The immune system relies on two separate types of immune responses: innate immunity and acquired immunity. T cells with innate immunity, including the gamma delta T cells, function as the immune system's "first line of defense” against foreign microbes, kicking in within hours of infection. T cells that are part of the acquired immune response then take center stage, playing a crucial role in eliminating foreign pathogens once an infection has developed. Acquired immunity takes time to mature, anywhere from days to weeks. It is the more effective of the two immune responses because it not only recognizes and attacks specific protein sequences of the foreign intruder, it also ‘remembers' them.

After an initial infection has been contained, these T cells switch roles and become ‘memory cells,' according to co-author Dr. Norman L. Letvin, of Beth Israel Deaconess Medical Center (Boston, MA, USA). "They then quietly ‘hang out' in the background until another infection develops, and then these memory cells respond very quickly and forcefully to ward off the new infection.”

Although evidence had existed that the gamma delta T cells provided protection against a range of infections, the immune responses of these cells had not been analyzed in detail. In the new study, lead author Dr. Zheng Chen and colleagues used macaque monkeys to study them. They injected macaques with BCG, bacteria closely related to the tuberculosis bacteria, and then evaluated their T cell memory response when the animals were challenged with a fresh injection. As early as four to six days after the second BCG inoculation, there was a marked expansion of the gamma delta T cells in the blood of the monkeys, which was two to nine times as great as the expansion during the primary infection. Furthermore, the authors found that the expansion of the cells lasted as long as seven months after the second inoculation.

"This study, for the first time, shows that this population of gamma delta T cells straddles the boundaries between innate and more mature immunity, suggesting that innate and acquired immunity cannot always be easily differentiated, said Dr. Letvin. "Not only do these T cells have memory capabilities, but the monkeys are calling upon them to fight infection.”