National Institute of Allergy andInfectious Diseases (NIAID) http://www.niaid.nih.gov
FOR IMMEDIATE RELEASE
Monday, Nov. 19, 20015:00 p.m.
New research suggests that HIV-specific T cells persist in infected individuals, but high virus levels can diminish the ability of those cells to respond to infection. The report sheds new light on how HIV evades the immune system and establishes long-term infections. The research appears in the November 20, 2001 issue of the Proceedings of the National Academy of Sciences.
"HIV infection not only destroys the body's resistance to other pathogens, but it can manipulate the immune system for its own survival," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID). "This research provides some important clues to how the virus accomplishes that goal."
In chronic viral infections, CD4+ T cells are required for the immune system to keep virus levels in check. In HIV-infected people, however, few anti-HIV CD4+ T cells proliferate when exposed to viral proteins. Researchers have not known if the absence of a proliferative T-cell response occurs because the virus destroys or merely inactivates HIV-specific CD4+ T cells.
NIAID's Andrew McNeil, M.D., and Mark Connors, M.D., led a study to answer that question. The investigators studied the T cells of three groups of patients: those with progressive HIV infection; a rare subset of individuals with long-term, untreated infection but with viral RNA levels consistently below the level of detection (long-term nonprogressors); and patients on antiretroviral therapy who stopped taking their drugs long enough for virus levels to rebound.
All three groups had equal numbers of HIV-specific CD4+ T cells, indicating the cells were not destroyed by the virus. The HIV-specific CD4+ T cells of people with progressive disease, however, did not respond to the virus by proliferating, suggesting they had somehow been turned off.
To examine the cause and effect relationship between proliferative T-cell responses and immune control over the virus, Drs. McNeil, Connors, and their colleagues turned to the patients who showed anti-HIV T-cell proliferation while taking antiretroviral drugs. The investigators reasoned that if those T cells were keeping HIV levels low, they should continue to do so even if therapy were interrupted. When the researchers stopped the drugs, however, virus levels rebounded in each of the patients. In those individuals, anti-HIV CD4+ T cells were present but lost their ability to proliferate as virus levels increased. Furthermore, the cells maintained their inactive state until antiretroviral drugs brought virus levels back under control.
The results suggest that the loss of HIV-specific T-cell proliferation may not be a cause, but rather is an effect, of high virus levels. Such proliferation, which is present in long-term nonprogressors, therefore does not necessarily predict immune control over the virus.
"This presents a good news/bad news scenario," says Dr. Connors. "The good news is that HIV-specific CD4+ T cells are not completely deleted; the bad news is that measuring the activity or even the frequency of those cells is not necessarily a good predictor of long-term virus control."
The results suggest that long-term interruptions in antiretroviral therapy may not be the best way to stimulate anti-HIV immune responses. The results also provide some clues to how HIV disrupts the immune response to itself and responses to other pathogens.
Copies of the research paper are available from the PNAS news office at (202) 334-2138 or by e-mail from firstname.lastname@example.org.
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Last Updated November 19, 2001