Microbiology's founding father, Louis Pasteur, already knew the trick: Adding a pinch of nonspecific, heat-killed bacteria makes any vaccine much more potent. Now immunologists have, at last, found a gene through which such "impurities" work their magic. The results, reported in the May issue of Nature Immunology, also shed light on how the same gene causes certain leukemias.
When a vaccine is administered--or when pathogens infect our bodies--these invaders are detected by T cells. When they encounter snippets of the pathogens' proteins, called antigens, the T cells start to divide rapidly, churn out chemical messengers and differentiate, for instance into T killer cells. Once the infection begins to wane, however, they kill themselves. But they leave behind a small number of memory T cells to protect the body from future attacks by the same pathogen.
Vaccine makers take advantage of this phenomenon. Adding heat-killed bacteria--called adjuvants--causes mild inflammations, thereby boosting the life expectancy of antigen-activated T cells. That leads to an increased number of memory T cells and thus a better vaccine. But nobody really knew how adjuvants did this.
The answer comes courtesy of a technology called gene chips. Philippa Marrack and her colleagues at the National Jewish Medical and Research Center in Denver used the chips to study 6400 genes that turn on when T cells encounter a bacterial antigen. They found only 23 genes that were switched on by two common kinds of adjuvants. Of those, a gene called Bcl-3 was particularly interesting, says Marrack, because it belongs to a family of proteins known to play a role in cell survival. Indeed, when the researchers tricked activated T cells into overproducing Bcl-3, about three times as many cells survived. Bcl-3, Marrack concludes, "somehow interferes with the cell death machinery" in activated T cells.
An important implication of the finding is that it also explains some puzzling features of leukemias caused by Bcl-3 abnormalities, such as chronic lymphocytic leukemia (CLL), says Andreas Strasser, an immunologist at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia. In contrast to other leukemias, CLL cancer cells don't divide very rapidly, but they are very hard to kill with chemotherapy, says Strasser. The study suggests that this may be because of their increased survival capacity, he says.