Important note: Information in this article was accurate in January 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, January 18, 1999
Daniel J. DeNoon, Senior Editor
There is a dramatic increase in HIV infected CD4(+) T cells in patients with their own culture-enhanced HIV specific CD8(+) cytotoxic T-lymphocytes (CTLs). This finding underscores the importance of CTLs for control of HIV infection, and has important implications for HIV vaccine development.
But the effect of these costly infusions wears off within a week, apparently because of insufficient assistance by HIV specific CD4(+) T-helper cells. Still, University of Washington researchers Scott J. Brodie, Stanley R. Riddell, and colleagues remain optimistic that help can be found.
"These results provide direct evidence that HIV specific CTLs target sites of HIV replication and mediate antiviral activity, and indicate that the development of immunotherapeutic approaches to sustain a strong CTL response to HIV may be a useful adjunct to treatment of HIV infection," Brodie et al. wrote.
They reported their findings in the journal Nature Medicine ("In Vivo Migration and Function of Transferred HIV-1 Specific Cytotoxic T Cells," Nature Med, 1999;5(1):34-41).
In order to track the infused cells, Brodie et al. genetically modified them to express the neomycin phosphotransferase gene.
The studies showed that the CTL travelled to sites of primary HIV infection in the lymph nodes and that they retained their lytic function. Infusion of the cells often resulted in a decline of HIV infected CD4(+) T cells to undetectable levels - an unfortunately transient effect
Individuals who remain asymptomatic despite long-term HIV infection maintain high levels of both CD8(+) and CD4(+) HIV specific T cells. Like most individuals with HIV infection, the study subjects lacked CD4(+) T-helper responses to HIV.
"Strategies to provide help to transferred CD8(+) CTLs, such as concomitant IL-2 infusions, concurrent adoptive transfer of HIV specific CD4(+) T-helper clones genetically modified to resist HIV infection, or genetic modification of the CD8(+) CTLs to function in a CD4 deficient environment should improve CTL survival and elucidate the therapeutic potential of CTLs for controlling progression of HIV infection," Brodie et al. suggested.
This study was supported by funds from the National Institutes of Health and the Pediatric AIDS Foundation.
The corresponding author for this study is Stanley R. Riddell, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D3-100, Seattle, Washington 98109.
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