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.