New model could show how immune system is thwarted by HIV and cancer
BOSTON-November 22, 1999-Researchers at the Center for Blood Research and Harvard Medical School report in the November 23 Proceedings of the National Academy of Sciences the development of an animal model that literally illuminates one of the most dramatic and, until now, obscure events in the body: how the immune system turns immature T cells into specialized killer, or cytotoxic, T cells, capable of seeking out and destroying cells maimed by cancer and infection.
"Now, we have a model that makes it possible to look at a unique and important subset of cells; first to identify it and then analyze it in novel ways," says Ulrich von Andrian, MD, PhD, HMS associate professor of pathology. "This system might allow us to get a better understanding of what provides the T cells' license to kill," he says. Ultimately, the model could be used to clarify such diseases as cancer and AIDS. Some researchers have suspected that viruses and tumor cells may thwart the immune system by taking away T cells' license to kill-that is, by sabotaging the cellular machinery that enables them to attack unwanted cells.
"During the initial stages of an HIV infection, there are lots of cytotoxic T cells in the body but, for some reason, they are not able to contain the infection," says N. Manjunath, PhD, research fellow, and lead author of the study. "Is there a defect in these cells? Understanding normal differentiation with our new model, we might help answer this question."
One of the biggest obstacles to understanding this crucial transformation has been spotting members of this elite corps in large enough numbers to study them. Relatively rare-white blood cells in general number about one in one thousand cells in the bloodstream-T cells also move with the same velocity as other cells in the blood so they tend to get lost in the crush.