AIDSWEEKLY Plus; Monday, January 12, 1998.
Daniel J. DeNoon, Senior Editor
This partial activation is doubly dangerous for T cells: not only does it render them susceptible to HIV infection, but it marks them for elimination by apoptosis.
"Our studies suggest that dysfunction, hyperactivation, and susceptibility to apoptosis, as observed with T cells isolated from HIV infected individuals, may be at least in part a consequence of abnormal function of ACs," wrote researchers Mei X. Wu and Stuart F. Schlossman of Harvard's Dana-Farber Cancer Institute.
Wu and Schlossman conducted experiments in which they exposed primary ACs to recombinant HIV-1 Tat protein. They reported their findings in the Proceedings of the National Academy of Sciences ("Decreased Ability of HIV-1 Tat Protein-Treated Accessory Cells To Organize Cellular Clusters Is Associated with Partial Activation of T Cells," PNAS, 1997;94:13832-7).
The ability of HIV to infect ACs - dendritic cells, monocytes, and macrophages - is a major feature of human HIV-1 infection. Chimpanzees infected with HIV-1 generally do not develop disease; HIV- 1 is incapable of infecting chimpanzee ACs. SIV strains capable of infecting macrophages cause disease in primates; SIV mutants incapable of infecting macrophages do not (reviewed in Balter, Science, 1996;274:1464-5).
The ACs exposed to Tat (Tat-ACs) by Wu and Schlossman acted very much like Tat itself in that it inhibited some but not all T-cell proliferative responses.
"The similarity underscored the importance of ACs in Tat protein- induced immunosuppression," Wu and Schlossman commented. "Our results indicate that Tat-AC-induced inhibition occurs independent of antigen processing and presentation by ACs."
The researchers showed that Tat-ACs are impaired in their ability to organize T-cell clusters, which results in incomplete T-cell activation.
"The partial activation of T cells is believed to be a critical factor for the maintenance of the infectious state, as HIV cannot infect resting T cells," they wrote.
Wu and Schlossman noted that the amount of circulating Tat protein in HIV infected individuals is very low. But they suggested that active HIV infection of ACs and phagocytosis of infected cells by macrophages may result in significant AC exposure to Tat. This exposure would be particularly high in the lymph nodes, and the researchers pointed out that activated ACs are seen in the lymph nodes of HIV infected but not normal individuals.
"The studies ... suggest a relationship between [HIV] infection of ACs and induction of abnormalities in T cells, which is consistent with animal models of AIDS and should provide additional strategies for effective HIV vaccine design," Wu and Schlossman concluded.
An earlier study at Dana-Farber Cancer Institute by Chiang J. Li and colleagues showed that Tat itself can cause partial T-cell proliferation (PNAS, 1997;94:81160-20).
"HIV-1 has evolved a self-perpetuating mechanism to actively generate cells permissive for productive and cytopathic infection," Li et al. wrote. "This mechanism provides a reliable way for HIV-1 to compensate for the rapid destruction of activated permissive lymphocytes during the highly cytopathic infection."
The Wu and Schlossman study was supported by National Institutes of Health Grants p30AI28691, AI12069, and CA-34183.
The corresponding author for this study is Mei X. Wu, Division of Tumor Immunology, Room 751, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA 02115. E-mail: <mei@mbcrr.harvard.edu>.
980112
AW980106
Copyright © 1998 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.
Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588 http://www.newsfile.com
AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 1998. This material is designed to support, not replace, the relationship that exists between you and your doctor.
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1980, 1998. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .