Two Cytokines Regulate Development of Immune System Memory Cells

The process of developing new vaccines should be facilitated by the discovery that two different cytokines regulate the formation of the CD8+ T-cells that "remember” pathogens and allow the immune system to quickly respond to any subsequent infection.

Investigators from the University of Texas Southwestern Medical School (Dallas, USA) studied how two cytokines, interleukin-21 (IL-21) and interferon, affected the development of immune T-cells in response to infection. They reported in the May 28, 2009, issue of the journal Blood that IL-12 exclusively promoted the development of interferon-gamma and tumor necrosis factor (TNF) secreting T effector memory (TEM) cells, whereas interferon drove the development of T central memory (TCM) cells.

The development of TEM and TCM was linked to cell division. In rapidly dividing cells, IL-12 programmed TEM through induction of the IL-12 receptor beta-2. In contrast, interferon regulated TCM development by slowing the progression of cell division in a subpopulation of cells that selectively expressed elevated interferon receptor-2. In the presence of both IL-12 and interferon, these cytokine signals promoted the simultaneous development of both TCM and TEM.

"Until now, no innate signals have been identified that regulate the development of memory cells,” said senior author Dr. David Farrar, assistant professor of immunology at the University of Texas Southwestern Medical Center. "Our study is the first to identify the signals that promote the development of these memory cells when you first get infected. Regardless of the precise mechanism, what we know now is that you can develop both long-term and immediate memory cells at the same time.”

"There are some vaccines that are extremely effective, while others are only moderately effective,” Dr. Farrar said. "If we can isolate pools of antigen-specific memory cells, we should be able to determine what it is about those pools of memory cells that is different between an extremely effective vaccine and one that's not so effective. If we can figure that out, then we can start to think about altering our approach to vaccinating based on the different type of microorganism that we're trying to vaccinate against.”

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University of Texas Southwestern Medical School