By David N. Leff

Creutzfeldt-Jakob disease (CJD) was a rare, fatal brain infection that traditionally struck down only the elderly. Because it took years to reach lethality, CJD was attributed to a "slow virus."

So was kuru, a brain disorder that certain tribes in New Guinea suffered after eating the brains of their enemies. Their own brains, and those of CJD victims, were punched full of holes, and resembled a sponge.

The same cerebral hallmark perforated the brains of sheep and goats, that madly scraped their necks against trees and fence posts. So their affliction got the name "scrapie." Then when British cattle acquired epizootic dementia in the mid-1980s, their affliction became known as "mad cow disease" - bovine spongiform encephalopathy. It was surmised that these herds caught the infection from the body parts of scrapie-carrying sheep, ground up in cattle feed. By then, "slow viruses" no longer were blamed. Instead, prions, discovered in 1982, proved to the perpetrators of scrapie, mad cow disease and CJD.

Within the past decade, 56 people in Britain, two in France and one in Ireland have died of what is now called "variant" Creutzfeldt-Jakob disease. That variance is the fact that these victims range in age from 13 to 43, whereas traditional "sporadic" CJD strikes down people over 50. The variant CJD victims had presumably eaten beef from mad cows.

Prions - the word stands for "proteinaceous infectious agent" - are the tiniest proteins in mammalian cells and tissues. Their normal version is called PrPr; the deadly, infective form, PrPr^SC. To study prion diseases, scientists have infected strains of mice with full-blown scrapie. Their latest finding appears in Science, dated May 19, 2000, under the title: "Impaired prion replication in spleens of mice lacking functional follicular dendritic cells."

Its senior author is molecular biologist Charles Weissmann, at the University of Zurich, Switzerland. He is regarded as a founding father of biotechnology, and a ranking prion researcher.

The immune system's follicular dendritic cells (FDCs) are top-gun catchers of antigens, or antigen fragments, on invading infective pathogens. They bring these antigenic molecules to the attention of antibody-generating B cells and cell-slaying T cells in the body's lymph nodes. (See BioWorld Today, May 10, 1999, p. 1.)

The Science paper's co-authors report that another mission of FDCs is to produce prions, which they found in the spleens, but not the lymph nodes, of scrapie mice. To mature and fulfill their role as star antigen-presenters, FDCs need the help of B cells that carry a lymphotoxin signaling molecule on their surface. When the researchers deactivated these with lymphotoxin receptors, FDCs disappeared and pathogenic PrPr^SC prions stopped accumulating. The co-authors speculate, in conclusion, that long-term treatment with the lymphotoxin-deactivating receptor "could retard" progression of prion-related neuroinvasive diseases.

On a related topic, immunologists and geneticists at Memorial Sloan-Kettering Cancer Center in New York have devised a gene-therapy strategy to artificially goad the immune system into stronger action against tumors and infective agents. By inserting human proteins into cultured mouse cells, they created artificial cells that mimic the ability of natural antigen-presenting cells to galvanize the immune system's killer T cells into acting against influenza viruses or tumor cells.

But purifying antigen-presenting dendritic cells from bone marrow or blood is a labor-intensive chore. An article in Nature Biotechnology for April 2000 offers a way out, titled "Induction of human cytotoxic T lymphocytes by artificial antigen-presenting cells." It authors engineered mouse fibroblasts to express a cocktail of immune system cells that orient foreign antigens so T cells can recognize them. These artificial antigen-presenting cells, they point out, can be grown in the laboratory and "used to stimulate T cells of any patient of a given human leukocyte antigen (HLA) type."