"Hair-Trigger" Cells Critical in AIDS Virus Escape

May 3, 2002 WNPRC News

MADISON-AIDS researchers at the Wisconsin Primate Research Center have narrowed in on a type of cell that kills all virally-infected cells it can recognize, according to findings published in the May issue of Nature Medicine.

These cells-called high avidity CTLs, or "hair trigger" CTLs-were present in almost all AIDS virus infected animals. Yet they had not been previously characterized. The reason for this, according to David Watkins, senior scientist at the Primate Center and professor of pathology at the University of Wisconsin-Madison, is that the cells rapidly select for variant viruses not recognized by the immune system.

Although his team's previous work (Nature 2000) showed that CTL selected for viral variants during early AIDS-virus infection in rhesus macaques, Watkins said he had no idea how commonly this occurs.

"The hair-trigger CTLs we identified resulted in viral escape in 19 out of 21 monkeys studied," Watkins said. "While others have shown that these hair-trigger CTLs exist as part of the immune response to other viruses, we were amazed that their presence in an animal model of HIV was linked so closely with rapid viral escape."

Researchers should be looking for these same sorts of responses in HIV, added David O'Connor, assistant scientist at the center. "Until now, it has been presumed that all CTLs are created equal," he said. "They are not. Some select for escape variants, others do not. Some have hair trigger responses, others do not. People designing effective vaccines or therapies need to be cognizant of these very real differences."

The link between hair-trigger CTL and AIDS-virus infection is not absolute, as evidenced by the fact that two of the 21 monkeys did not show the hair trigger attack response. "There are certainly other immune responses entering into play," said O'Connor. "But now the AIDS research community has an even stronger tool with which to pursue vaccine development in monkeys and humans."

In fact, one of the study's co-authors, Todd Allen, is doing just that. Allen departed the Watkins lab last year to work on early HIV infection studies and treatments with Bruce Walker at Boston's Massachusetts General Hospital.

"Todd has just begun to look at high avidity CTLs in AIDS patients," O'Connor said. "Dr. Walker has a good record of delivering effective, strong therapies early on to people who are found to be HIV-positive within a few weeks of infection."

Other major contributors to the research included Thorsten Vogel, Bianca Moth, Ivna DeSouza, Ed Dunphy, and Nancy Wilson at the Primate Center; and Austin Hughes at the University of South Carolina. The National Institutes of Health and the Elizabeth Glaser Pediatric AIDS foundation funded the research.

Reference: O'Connor DH, Allen TM, Vogel TU, Jing P, DeSouza IP, Dodds E, Dunphy EJ, Melsaether C, Mothé B, Yamamoto H, Horton H, Wilson N, Hughes AL, Watkins DI. Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection. Nature Medicine. May; 8(5). 2002.

-J. Lenon