Memory T Cells Don't Need to Rehearse Their Lines

Scientists have long debated whether an immune cell needs to be regularly reminded of which particular germs to fight or whether its memory is ever-lasting. Two reports in tomorrow's issue of Science (pp. 1377 and 1381) now bolster the notion that at least some immune cells never forget.

The immune cells in question, T cells, spring into action to kill infected cells or orchestrate other immune responses when other cells "present" them with an appropriate antigen--a fragment of a viral protein, say--together with a so-called MHC protein. Some T cells then retain the memory of this encounter, enabling them to respond immediately if the virus invades again--an ability that is the basis of vaccination.

For their work, Rafi Ahmed of Emory University in Atlanta and his colleagues used killer T cells, which destroy cells infected by viruses. After vaccinating mice with a common pathogenic virus, the researchers took killer T cells from the animals and transferred them to mice with no T cells of their own. Some of these mice also lacked a protein which helps transport the MHC antigen needed for antigen presentation to killer T cells to the cell surface. As a result, the transplanted killer T cells got no antigen stimulation from their new hosts. Even so, 10 months later, the mice without the delivery protein had as many memory T cells as did the mice with the protein--strong evidence that memory cells can persist, and still recognize their targets, without a reminder from the antigen.

Another team, led by Susan Swain of the Trudeau Institute in Saranac Lake, New York, studied T helper cells, which jump-start other immune cells. The team introduced an antigen to purified T helper cells, then a few days later, transplanted the cells--presumably before they had time to develop a memory of the antigen--into mice lacking the MHC protein necessary for stimulating T helper cells. Memory T helper cells developed in the animals and again persisted without further prodding from antigens.

For many, although not all, immunologists, the findings cast a final verdict on the long-standing controversy. "These two papers nail it down pretty firmly that you don't need antigen" or other known signals to maintain T cell memory, says Peter Beverley of the Edward Jenner Institute for Vaccine Research in Compton, U.K.