Immune Cells May Play Previously Unrecognized Role in Inflammation in HIV/AIDS
May 28, 2013 - 1:33:12 PM
The low numbers of white blood cells, known as CD4+CD73+ T cells - named for the expression of certain proteins and enzymes on their surface - persist even when HIV is well-controlled with medications. The results of the study, funded by the National Institutes of Health (NIH) and now available online, will be reported in an upcoming issue of the journalAIDS.
"People with well-controlled HIV have been shown to have higher rates of chronic, non-AIDS-related diseases, such as cardiovascular disease. This is believed to be related to the persistent immune activation and inflammation associated with chronic HIV infection," said corresponding author Bernard J.C. Macatangay, M.D., Division of Infectious Diseases/HIV/AIDS Program, Pitt School of Medicine. "We believe that the depleted CD4+CD73+ T cells play an important role in this inflammation."
The study was done in men from the Pittsburgh site of the Multicenter AIDS Cohort Study, an NIH-funded, ongoing 30-year investigation of the natural history of HIV infection in men who have sex with men. Blood samples were analyzed from 36 men positive for HIV, some who had consistently taken a medication regimen to suppress the virus and some who had not, along with 10 HIV-negative controls.
The body has ways to decrease and control inflammation through different regulatory mechanisms. One of these is through the production of adenosine, a biochemical compound that may have anti-inflammatory properties. CD73 is an enzyme that is important in the production of adenosine. In the HIV-positive men, the study found that the CD4+CD73+ T cells are depleted and, despite treatment, do not increase to levels seen in uninfected individuals. The Pitt researchers found an association between the low levels of CD4+CD73+T cells and higher levels of immune activation and inflammation in the study participants.
"This inflammation issue is similar to that seen in cancer patients," said co-author Theresa Whiteside, Ph.D., professor of pathology, immunology and otolaryngology at Pitt's School of Medicine and a member of Pitt's Cancer Institute. "The suppression pathways we explore in this study have similarities to those that we have recently linked to immune suppression in cancer."
Scientists are not sure why this pathway remains disrupted in people with very well-controlled HIV. One hypothesis is that HIV-positive patients do not completely recover from damage done during the first few weeks of infection in their gut mucosa, which hosts the body's largest population of immune cells.
"Significant damage occurs very early in infection, while they are still asymptomatic and do not even know they have the virus," said Dr. Macatangay. "This is why it is important that we continue to examine the role of CD4+CD73+ T cells and adenosine in increased inflammation among HIV/AIDS patients and look for ways to repair the damage to the natural pathways by which these cells act."
Additional study co-authors include Patrick J. Schuler, M.D., Ph.D., of the University of Ulm in Germany; Zenichiro Saze, M.D., Ph.D., Edwin K. Jackson, Ph.D., Sharon A. Riddler, M.D., Benedict B. Hilldorfer and John W. Mellors, M.D., all of Pitt's School of Medicine; and William G. Buchanan, M.M., and Charles R. Rinaldo, Ph.D., both of Pitt's Graduate School of Public Health.
This study was supported by National Institutes of Health grants PO1 CA109668, U01 AI035041, DK079307, T32 AI065380, and HHSN261200800001E.
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About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
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