AIDSWEEKLY Plus; Monday, December 7, 1998
Daniel J. DeNoon, Senior Editor
CD8(+) from healthy HIV infected individuals is able to suppress HIV in CD4(+) T-cell cultures without killing infected cells. This activity is mediated by a soluble factor or factors and does not depend on human leukocyte antigen (HLA) relatedness between the CD8(+) effector and CD4(+) target cells.
But new evidence suggests that genetic factors are able to regulate this phenomenon.
"The extent of this antiviral CD8(+) T-cell noncytotoxic response is dependent on the genetic relatedness between the effector and target cells, but not necessarily on HLA class I or class II determinants," concluded University of California, San Francisco researchers Carl E. Mackewicz, Marvin R. Garovoy, and Jay A. Levy.
Mackewicz et al. reported their findings in the Journal of Virology ("HLA Compatibility Requirements for CD8(+) T-Cell-Mediated Suppression of Human Immunodeficiency Virus Replication," J Virol, 1998;72(12):10165-70).
CD8+ T-cell-mediated suppression of HIV has been linked to the cells' expression of the anti-HIV (beta)-chemokines RANTES, MIP- 1(alpha) and MIP-1(beta) (Cocchi et al., Science, 1995;270:1811), and the C-X-C chemokine SDF-1.
Levy and co-workers are convinced, however, despite the contribution made by (beta) chemokines, this inhibitory activity is due mainly to a long-sought, as-yet-unidentified substance they have dubbed CD8+ cell antiviral factor, or CAF (for an account of the CAF/chemokine debate between the Levy and Robert Gallo camps see AIDS Weekly Plus, December 23/30, 1996).
The Levy team has listed four principal characteristics of CD8(+) noncytopathic suppression of HIV:
* It does not involve the destruction of target cells.
* It does not modulate the activation of target CD4+ cells.
* Its effector phase is independent of major histocompatibility complex (MHC) restriction.
* It is at least in part mediated by a novel soluble factor not identical to any other known cytokines or chemokines.
In their current study, Mackewicz et al. suggested that assays of CD8(+) noncytotoxic inhibition of HIV may underestimate the potency of the phenomenon when genetically mismatched effector and target cells are used.
They suggest that the new findings may lead to improved treatments for HIV infection.
"A better understanding of the regulation of this CD8(+) T-cell anti-HIV activity could lead to improving or at least maintaining this antiviral response," Mackewicz et al. wrote.
These studies were funded by a grant from the National Institutes of Health and the Histocompatibility Fund.
The corresponding author for this study is Jay A. Levy, Department of Medicine, School of Medicine, University of California, San Francisco, California 94143-1270. Phone: (415)476-4071. Fax: (415)476-8365. Email: <jalevy@itsa.ucsf.edu>.
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