AIDSWEEKLY Plus; Monday, September 7 & 14, 1998
Daniel J. DeNoon, Senior Editor
Thai sex workers who resist HIV infection have high levels of monocyte-derived factors that suppress HIV infection, according to Salvatore T. Butera of the U.S. Centers for Disease Control and Prevention (CDC).
"Monocyte-derived factors that suppress post-integrated HIV expression could represent a new class of soluble regulators," Butera suggested. "Although the production of soluble factors capable of suppressing HIV replication cannot fully explain the mechanism of protection from infection, when combined with other local and systemic viral specific and nonspecific responses, an ability to abort HIV infection may result."
Butera presented the findings at the 12th World AIDS Conference, held June 28-July 3, 1998, in Geneva, Switzerland.
The CDC research team obtained peripheral blood mononuclear cells (PBMC) from eight highly-exposed, persistently seronegative (HEPS) female sex workers in Chiang Rai, Thailand. The subjects are members of a cohort identified by Timothy Mastro and colleagues in a collaborative study by the CDC and the Thai Ministry of Public Health.
Control PBMC were obtained from HIV positive sex workers and HIV negative low-risk individuals.
The researchers sorted subjects' PBMC according to cellular differentiation marker type: CD4, CD8, CD14, or CD19 positive cells. They then analyzed supernatants from the separated PBMC cultures for anti-HIV activity at different time points.
"Supernatants derived from the culture of exposed/uninfected PBMCs demonstrated a marked capability to suppress HIV replication in the chronically; infected myeloid cell bioassay," Butera reported. "Although individual variation was evident, overall exposed/uninfected cultures produced higher levels of suppressive factors than did HIV negative control cultures."
The mean percentage of inhibition was 49 percent in the exposed/uninfected group and 14 percent in the uninfected group. Interestingly, the HIV infected subjects had PBMC activity similar to that seen in the exposed/uninfected subjects.
Most of the suppressive activity came from the CD14(+) monocyte- derived PBMC fraction. Oddly, given the demonstrated ability of CD8(+) cells to produce a soluble anti-HIV factor in other studies, no suppression occurred with the CD8(+) supernatants.
In another AIDS conference presentation, CDC researcher Busarawan Sriwanthana found that HEPS women have HIV specific cytotoxic T- lymphocyte (CTL) activity.
"These data suggest that, in the absence of HIV receptor abnormalities which prevent cellular infection, exposed individuals may remain uninfected or may clear HIV infected cells through the effects of HIV specific CTL," Sriwanthana observed. "These data also emphasize the importance of CTL induction as a desirable component of a protective HIV vaccine-induced response."
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